The observed variant NM_000151.3:g.230_231delGT/p.Trp50CysfsTer10 is a two base pair deletion in exon 1 of the G6PC gene. It has not been reported in the 1000 Genomes and ExAC databases. It has been reported as a common mutation in Indian patients with glycogen storage disease type Ia by Meaney.C et al (2001). The in silico prediction of this variant is disease causing by MutationTaster2. The reference codon is conserved across species.
ClinVar Genomic variation as it relates to human health
NM_000151.4(G6PC1):c.150_151del (p.Trp50fs)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(4)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic/Likely pathogenic
4
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000151.4(G6PC1):c.150_151del (p.Trp50fs)
Variation ID: 370671 Accession: VCV000370671.4
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 17q21.31 17: 42901026-42901027 (GRCh38) [ NCBI UCSC ] 17: 41053043-41053044 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 6, 2017 Feb 14, 2024 Feb 16, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000151.4:c.150_151del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000142.2:p.Trp50fs frameshift NM_000151.4:c.150_151delGT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001270397.2:c.150_151del NP_001257326.1:p.Trp50fs frameshift NC_000017.11:g.42901026_42901027del NC_000017.10:g.41053043_41053044del NG_011808.1:g.5229_5230del LRG_147:g.5229_5230del - Protein change
- W50fs
- Other names
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- Canonical SPDI
- NC_000017.11:42901025:GT:
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Unknown function
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| G6PC1 | - | - |
GRCh38 GRCh37 |
568 | 575 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Feb 16, 2023 | RCV000409261.5 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Mar 02, 2019)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV000891162.1
First in ClinVar: Jan 06, 2017 Last updated: Jan 06, 2017 |
Comment:
The observed variant NM_000151.3:g.230_231delGT/p.Trp50CysfsTer10 is a two base pair deletion in exon 1 of the G6PC gene. It has not been reported in the 1000 … (more)
The observed variant NM_000151.3:g.230_231delGT/p.Trp50CysfsTer10 is a two base pair deletion in exon 1 of the G6PC gene. It has not been reported in the 1000 Genomes and ExAC databases. It has been reported as a common mutation in Indian patients with glycogen storage disease type Ia by Meaney.C et al (2001). The in silico prediction of this variant is disease causing by MutationTaster2. The reference codon is conserved across species. (less)
Clinical Features:
Hypertriglyceridemia (present) , Hepatomegaly (present) , Xanthelasma (present) , Anemia (present)
Zygosity: Homozygote
Age: 0-9 years
Sex: female
Geographic origin: Gujarat, India
Method: DNA was used to perform targeted gene sequencing using a custom capture kit. Libraries were sequenced to mean >80-100X coverage on Illumina Sequencing Platform. Sequence obtained was aligned to a human reference genome (GRCh37/hg19) using BWA program and then analyzed using Picard and GATK version 3.6 to identify variants in the targeted genes relevant to the clinical indication.
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Likely pathogenic
(Mar 22, 2016)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000486049.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Lifecell International Pvt. Ltd
Accession: SCV003924084.1
First in ClinVar: May 13, 2023 Last updated: May 13, 2023 |
Comment:
A Homozygote Frameshift variant c.150_151delGT in Exon 1 of the G6PC1 gene that results in the amino acid substitution p.Trp50fs*10 was identified. The observed variant … (more)
A Homozygote Frameshift variant c.150_151delGT in Exon 1 of the G6PC1 gene that results in the amino acid substitution p.Trp50fs*10 was identified. The observed variant is novel in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic/Likely Pathogenic [Variation ID: 370671]. The observed variation has been previously reported in Glycogen storage disorder type I patients (Meaney C, et.al, 2001). For these reasons, this variant has been classified as Pathogenic. (less)
Zygosity: Homozygote
Ethnicity/Population group: Asian
Geographic origin: India
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Pathogenic
(Feb 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004297778.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 370671). This sequence change creates a premature translational stop signal (p.Trp50Cysfs*10) in the G6PC gene. It … (more)
ClinVar contains an entry for this variant (Variation ID: 370671). This sequence change creates a premature translational stop signal (p.Trp50Cysfs*10) in the G6PC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in G6PC are known to be pathogenic (PMID: 8182131). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with glycogen storage disease type Ia (PMID: 11596659). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
Comment:
Comment:
A Homozygote Frameshift variant c.150_151delGT in Exon 1 of the G6PC1 gene that results in the amino acid substitution p.Trp50fs*10 was identified. The observed variant is novel in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic/Likely Pathogenic [Variation ID: 370671]. The observed variation has been previously reported in Glycogen storage disorder type I patients (Meaney C, et.al, 2001). For these reasons, this variant has been classified as Pathogenic.
Comment:
ClinVar contains an entry for this variant (Variation ID: 370671). This sequence change creates a premature translational stop signal (p.Trp50Cysfs*10) in the G6PC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in G6PC are known to be pathogenic (PMID: 8182131). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with glycogen storage disease type Ia (PMID: 11596659). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|---|---|---|---|
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Unknown function
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Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV000891162.1
|
|
Comment:
The observed variant NM_000151.3:g.230_231delGT/p.Trp50CysfsTer10 is a two base pair deletion in exon 1 of the G6PC gene. It has not been reported in the 1000 Genomes and ExAC databases. It has been reported as a common mutation in Indian patients with glycogen storage disease type Ia by Meaney.C et al (2001). The in silico prediction of this variant is disease causing by MutationTaster2. The reference codon is conserved across species.
Comment:
A Homozygote Frameshift variant c.150_151delGT in Exon 1 of the G6PC1 gene that results in the amino acid substitution p.Trp50fs*10 was identified. The observed variant is novel in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic/Likely Pathogenic [Variation ID: 370671]. The observed variation has been previously reported in Glycogen storage disorder type I patients (Meaney C, et.al, 2001). For these reasons, this variant has been classified as Pathogenic.
Comment:
ClinVar contains an entry for this variant (Variation ID: 370671). This sequence change creates a premature translational stop signal (p.Trp50Cysfs*10) in the G6PC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in G6PC are known to be pathogenic (PMID: 8182131). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with glycogen storage disease type Ia (PMID: 11596659). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| A common 2 bp deletion mutation in the glucose-6-phosphatase gene in Indian patients with glycogen storage disease type Ia. | Meaney C | Journal of inherited metabolic disease | 2001 | PMID: 11596659 |
| Identification of mutations in the gene for glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a. | Lei KJ | The Journal of clinical investigation | 1994 | PMID: 8182131 |
Text-mined citations for rs1057516674 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.