VCV000003499.2 - ClinVar

NM_024426.6(WT1):c.1036A>G (p.Ser346Gly)

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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_024426.6(WT1):c.1036A>G (p.Ser346Gly)

Variation ID: 3499 Accession: VCV000003499.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p13 11: 32400025 (GRCh38) [ NCBI UCSC ] 11: 32421571 (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	Apr 4, 2013	Apr 4, 2013	Dec 1, 1993

HGVS

Nucleotide	Protein	Molecular consequence
NM_024426.6:c.1036A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_077744.4:p.Ser346Gly	missense
NM_000378.6:c.985A>G	NP_000369.4:p.Ser329Gly	missense
NM_001198551.2:c.385A>G	NP_001185480.1:p.Ser129Gly	missense
NM_001198552.2:c.334A>G	NP_001185481.1:p.Ser112Gly	missense
NM_001367854.1:c.-153A>G		5 prime UTR
NM_001407044.1:c.1030A>G	NP_001393973.1:p.Ser344Gly	missense
NM_001407045.1:c.985A>G	NP_001393974.1:p.Ser329Gly	missense
NM_001407046.1:c.1036A>G	NP_001393975.1:p.Ser346Gly	missense
NM_001407047.1:c.913A>G	NP_001393976.1:p.Ser305Gly	missense
NM_001407048.1:c.985A>G	NP_001393977.1:p.Ser329Gly	missense
NM_001407049.1:c.985A>G	NP_001393978.1:p.Ser329Gly	missense
NM_001407050.1:c.862A>G	NP_001393979.1:p.Ser288Gly	missense
NM_001407051.1:c.274A>G	NP_001393980.1:p.Ser92Gly	missense
NM_024424.5:c.1036A>G	NP_077742.3:p.Ser346Gly	missense
NM_024425.2:c.970A>G	NP_077743.2:p.Ser324Gly	missense
NR_160306.1:n.1368A>G		non-coding transcript variant
NR_176266.1:n.1317A>G
NC_000011.10:g.32400025T>C
NC_000011.9:g.32421571T>C
NG_009272.1:g.40517A>G
LRG_525:g.40517A>G
LRG_525t1:c.1021A>G	LRG_525p1:p.Ser341Gly
LRG_525t2:c.385A>G	LRG_525p2:p.Ser129Gly

... more HGVS ... less HGVS

Protein change

S129G, S329G, S112G, S346G, S305G, S92G, S288G, S344G

Other names

WT1, SER273GLY

Canonical SPDI

NC_000011.10:32400024: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

ClinGen: CA016356 OMIM: 607102.0016 dbSNP: rs121907908 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 8401592 to determine the location of this allele on current reference sequence.

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.
WT1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	916	1675

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.
Mesothelioma	Pathogenic (1)	no assertion criteria provided	Dec 1, 1993	RCV000003673.5

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.
Pathogenic (Dec 01, 1993)	no assertion criteria provided Method: literature only	MESOTHELIOMA, SOMATIC Affected status: not provided Allele origin: somatic	OMIM Accession: SCV000023836.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (2) PubMed: 8298644‚ 4332312 Comment on evidence: Park et al. (1993) showed that the WT1 gene, in addition to being expressed in tissues of the genitourinary system, is also expressed at high … (more) Park et al. (1993) showed that the WT1 gene, in addition to being expressed in tissues of the genitourinary system, is also expressed at high levels in many supportive structures of mesodermal origin in the mouse. Furthermore, they described a case of adult human mesothelioma (156240) that contained a homozygous A-to-G transition resulting in a serine to glycine substitution at codon 273 (S273G). Normal tissue from the patient showed no evidence of this mutation, indicating that it was absent from the germline and arose as a somatic mutation within the tumor. Mesothelioma is a tumor derived from the peritoneal lining. The particular tumor studied was of the rare multicystic type which is not metastatic and has been classified as a hamartoma or a developmental abnormality of borderline malignancy (Salazar et al., 1972). Unlike most mesotheliomas, multicystic tumors are not associated with a history of asbestos exposure. Park et al. (1993) screened 32 specimens of asbestos-related mesothelioma and found no WT1 mutations. The ser273-to-gly mutation was the first reported outside the zinc finger domain that leads to an amino acid substitution rather than a termination codon. Codon 273 is highly conserved across species. Whereas wildtype WT1 represses transcription from the early growth response-1 (EGR1; 128990) promoter, following cotransfection into NIH 3T3 cells, Park et al. (1993) found that insertion of the ser273-to-gly mutation resulted in a WT1 protein that activated transcription from the EGR1 promoter. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Inactivation of WT1 in nephrogenic rests, genetic precursors to Wilms' tumour.	Park S	Nature genetics	1993	PMID: 8298644
Ultrastructure and observations on the histogenesis of mesotheliomas, "adenomatoid tumors", of the female genital tract.	Salazar H	Cancer	1972	PMID: 4332312

Text-mined citations for rs121907908 ...

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 05, 2022

ClinVar Genomic variation as it relates to human health

NM_024426.6(WT1):c.1036A>G (p.Ser346Gly)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs121907908 ...