VCV000374184.17 - ClinVar

NM_001174096.2(ZEB1):c.976C>T (p.Arg326Ter)

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.

(3)

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

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001174096.2(ZEB1):c.976C>T (p.Arg326Ter)

Variation ID: 374184 Accession: VCV000374184.17

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10p11.22 10: 31520308 (GRCh38) [ NCBI UCSC ] 10: 31809236 (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	Jan 13, 2017	Oct 20, 2024	Jun 1, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001174096.2:c.976C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001167567.1:p.Arg326Ter	nonsense
NM_001128128.3:c.925C>T	NP_001121600.1:p.Arg309Ter	nonsense
NM_001174093.2:c.913C>T	NP_001167564.1:p.Arg305Ter	nonsense
NM_001174094.2:c.922C>T	NP_001167565.1:p.Arg308Ter	nonsense
NM_001174095.2:c.772C>T	NP_001167566.1:p.Arg258Ter	nonsense
NM_001323638.2:c.319C>T	NP_001310567.1:p.Arg107Ter	nonsense
NM_001323641.2:c.319C>T	NP_001310570.1:p.Arg107Ter	nonsense
NM_001323642.2:c.319C>T	NP_001310571.1:p.Arg107Ter	nonsense
NM_001323643.2:c.319C>T	NP_001310572.1:p.Arg107Ter	nonsense
NM_001323644.2:c.319C>T	NP_001310573.1:p.Arg107Ter	nonsense
NM_001323645.2:c.319C>T	NP_001310574.1:p.Arg107Ter	nonsense
NM_001323646.2:c.319C>T	NP_001310575.1:p.Arg107Ter	nonsense
NM_001323647.2:c.319C>T	NP_001310576.1:p.Arg107Ter	nonsense
NM_001323648.2:c.319C>T	NP_001310577.1:p.Arg107Ter	nonsense
NM_001323649.2:c.319C>T	NP_001310578.1:p.Arg107Ter	nonsense
NM_001323650.2:c.319C>T	NP_001310579.1:p.Arg107Ter	nonsense
NM_001323651.2:c.319C>T	NP_001310580.1:p.Arg107Ter	nonsense
NM_001323652.2:c.319C>T	NP_001310581.1:p.Arg107Ter	nonsense
NM_001323653.2:c.319C>T	NP_001310582.1:p.Arg107Ter	nonsense
NM_001323654.2:c.319C>T	NP_001310583.1:p.Arg107Ter	nonsense
NM_001323655.2:c.319C>T	NP_001310584.1:p.Arg107Ter	nonsense
NM_001323656.2:c.319C>T	NP_001310585.1:p.Arg107Ter	nonsense
NM_001323657.2:c.319C>T	NP_001310586.1:p.Arg107Ter	nonsense
NM_001323658.2:c.319C>T	NP_001310587.1:p.Arg107Ter	nonsense
NM_001323659.2:c.319C>T	NP_001310588.1:p.Arg107Ter	nonsense
NM_001323660.2:c.319C>T	NP_001310589.1:p.Arg107Ter	nonsense
NM_001323661.2:c.319C>T	NP_001310590.1:p.Arg107Ter	nonsense
NM_001323662.2:c.319C>T	NP_001310591.1:p.Arg107Ter	nonsense
NM_001323663.2:c.319C>T	NP_001310592.1:p.Arg107Ter	nonsense
NM_001323664.2:c.319C>T	NP_001310593.1:p.Arg107Ter	nonsense
NM_001323665.2:c.319C>T	NP_001310594.1:p.Arg107Ter	nonsense
NM_001323666.2:c.319C>T	NP_001310595.1:p.Arg107Ter	nonsense
NM_001323671.2:c.319C>T	NP_001310600.1:p.Arg107Ter	nonsense
NM_001323672.2:c.319C>T	NP_001310601.1:p.Arg107Ter	nonsense
NM_001323673.2:c.319C>T	NP_001310602.1:p.Arg107Ter	nonsense
NM_001323674.2:c.751C>T	NP_001310603.1:p.Arg251Ter	nonsense
NM_001323675.2:c.709C>T	NP_001310604.1:p.Arg237Ter	nonsense
NM_001323676.2:c.934C>T	NP_001310605.1:p.Arg312Ter	nonsense
NM_001323677.2:c.931C>T	NP_001310606.1:p.Arg311Ter	nonsense
NM_001323678.2:c.700C>T	NP_001310607.1:p.Arg234Ter	nonsense
NM_030751.6:c.973C>T	NP_110378.3:p.Arg325Ter	nonsense
NC_000010.11:g.31520308C>T
NC_000010.10:g.31809236C>T
NG_017048.1:g.206136C>T

... more HGVS ... less HGVS

Protein change

R325*, R237*, R305*, R311*, R251*, R309*, R234*, R107*, R258*, R308*, R312*, R326*

Other names

Canonical SPDI

NC_000010.11:31520307:C:T

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: CA16043448 dbSNP: rs1057518956 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.
ZEB1		-	-	GRCh38 GRCh37	129	147

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.
Glaucoma Polymorphous corneal dystrophy Visual loss	Pathogenic (1)	criteria provided, single submitter	Jan 14, 2014	RCV000415113.2
not provided	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jun 1, 2023	RCV000599440.15

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 (Jan 14, 2014)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Glaucoma Polymorphous corneal dystrophy Visual loss Affected status: yes Allele origin: unknown	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV000493014.1 First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017
Pathogenic (Nov 08, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000709986.4 First in ClinVar: Apr 02, 2018 Last updated: Mar 04, 2023	Comment: Published functional studies demonstrate a damaging effect (Chung et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a … (more) Published functional studies demonstrate a damaging effect (Chung et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25190660, 27537263, 17935237, 19337156, 25525159) (less)
Pathogenic (Jun 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004033039.11 First in ClinVar: Sep 16, 2023 Last updated: Oct 20, 2024	Comment: ZEB1: PVS1, PM2, PS3:Supporting Number of individuals with the variant: 1

Comment:

Published functional studies demonstrate a damaging effect (Chung et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25190660, 27537263, 17935237, 19337156, 25525159)

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 rs1057518956 ...

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 Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_001174096.2(ZEB1):c.976C>T (p.Arg326Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1057518956 ...