VCV000618672.8 - ClinVar

NM_002109.6(HARS1):c.743A>G (p.Glu248Gly)

Germline

Classification

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.

(1)

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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002109.6(HARS1):c.743A>G (p.Glu248Gly)

Variation ID: 618672 Accession: VCV000618672.8

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q31.3 5: 140677407 (GRCh38) [ NCBI UCSC ] 5: 140056992 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Feb 18, 2019	Feb 18, 2019	Dec 12, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_002109.6:c.743A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002100.2:p.Glu248Gly	missense
NM_001258040.3:c.623A>G	NP_001244969.1:p.Glu208Gly	missense
NM_001258041.3:c.683A>G	NP_001244970.1:p.Glu228Gly	missense
NM_001258042.3:c.563A>G	NP_001244971.1:p.Glu188Gly	missense
NM_001289092.2:c.521A>G	NP_001276021.1:p.Glu174Gly	missense
NM_001289093.2:c.401A>G	NP_001276022.1:p.Glu134Gly	missense
NM_001289094.2:c.656A>G	NP_001276023.1:p.Glu219Gly	missense
NC_000005.10:g.140677407T>C
NC_000005.9:g.140056992T>C
NG_032158.1:g.18980A>G
LRG_1374:g.18980A>G
LRG_1374t1:c.743A>G	LRG_1374p1:p.Glu248Gly

... more HGVS ... less HGVS

Protein change

E248G, E134G, E188G, E208G, E174G, E219G, E228G

Other names

Canonical SPDI

NC_000005.10:140677406:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

dbSNP: rs1261330102 VarSome

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
Gene	OMIM	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.
HARS1		-	-	GRCh38 GRCh37	535	591

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.
not provided	Uncertain significance (1)	criteria provided, single submitter	Dec 12, 2017	RCV000757350.8

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.
Uncertain significance (Dec 12, 2017)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process) Method: clinical testing	Not Provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000885540.1 First in ClinVar: Feb 18, 2019 Last updated: Feb 18, 2019	Comment: The p.Glu248Gly variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. It … (more) The p.Glu248Gly variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. It is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP), and the Genome Aggregation Database (gnomAD). The glutamic acid at position 248 is weakly conserved considering 12 species (Alamut v2.10) and computational analyses of the effects of the p.Glu248Gly variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Glu248Gly variant with certainty. (less)

Comment:

The p.Glu248Gly variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. It is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP), and the Genome Aggregation Database (gnomAD). The glutamic acid at position 248 is weakly conserved considering 12 species (Alamut v2.10) and computational analyses of the effects of the p.Glu248Gly variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Glu248Gly variant with certainty.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs1261330102 ...

These 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 Mar 05, 2023

ClinVar Genomic variation as it relates to human health

NM_002109.6(HARS1):c.743A>G (p.Glu248Gly)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1261330102 ...