VCV000488617.3 - ClinVar

NM_016495.6(TBC1D7):c.747dup (p.Val250fs)

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.

(2)

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.

Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_016495.6(TBC1D7):c.747dup (p.Val250fs)

Variation ID: 488617 Accession: VCV000488617.3

Type and length

Duplication, 1 bp

Location

Cytogenetic: 6p24.1 6: 13306445-13306446 (GRCh38) [ NCBI UCSC ] 6: 13306677-13306678 (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 8, 2018	Nov 30, 2024	May 20, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_016495.6:c.747dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_057579.1:p.Val250fs	frameshift
NM_001143964.4:c.747dup	NP_001137436.1:p.Val250fs	frameshift
NM_001143965.4:c.747dup	NP_001137437.1:p.Val250fs	frameshift
NM_001143966.4:c.666dup	NP_001137438.1:p.Val223fs	frameshift
NM_001258457.3:c.609dup	NP_001245386.1:p.Val204fs	frameshift
NM_001318805.2:c.747dup	NP_001305734.1:p.Val250fs	frameshift
NM_001318809.2:c.747dup	NP_001305738.1:p.Val250fs	frameshift
NM_016495.5:c.747dup
NC_000006.12:g.13306449dup
NC_000006.11:g.13306681dup
NG_033862.1:g.27138dup

... more HGVS ... less HGVS

Protein change

V204fs, V223fs, V250fs

Other names

Canonical SPDI

NC_000006.12:13306445:TTTT:TTTTT

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

ClinGen: CA658683439 dbSNP: rs1554192525 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.
TBC1D7		-	-	GRCh38 GRCh37	-	149
TBC1D7-LOC100130357	-	-	-	GRCh38	-	153

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.
Macrocephaly	Pathogenic (1)	criteria provided, single submitter	Nov 8, 2017	RCV000578342.5
not provided	Uncertain significance (1)	criteria provided, single submitter	May 20, 2024	RCV004794417.1

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.
Pathogenic (Nov 08, 2017)	criteria provided, single submitter (Classification criteria August 2017) Method: clinical testing	Macrocephaly/megalencephaly syndrome, autosomal recessive (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München Accession: SCV000680401.1 First in ClinVar: Feb 08, 2018 Last updated: Feb 08, 2018	Zygosity: Homozygote Sex: female Tissue: blood
Uncertain significance (May 20, 2024)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV005415265.1 First in ClinVar: Nov 30, 2024 Last updated: Nov 30, 2024	Comment: Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in abnormal protein length as the last 44 amino acids … (more) Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in abnormal protein length as the last 44 amino acids are replaced with 30 different amino acids in a gene for which loss-of-function is not an established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge (less)

Comment:

Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in abnormal protein length as the last 44 amino acids are replaced with 30 different amino acids in a gene for which loss-of-function is not an established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge

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 rs1554192525 ...

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 Nov 30, 2024

ClinVar Genomic variation as it relates to human health

NM_016495.6(TBC1D7):c.747dup (p.Val250fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1554192525 ...