NM_024426.6(WT1):c.391C>T (p.Pro131Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 26, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001861942.4

Allele description [Variation Report for NM_024426.6(WT1):c.391C>T (p.Pro131Ser)]

NM_024426.6(WT1):c.391C>T (p.Pro131Ser)

Genes:

WT1:WT1 transcription factor [Gene - OMIM - HGNC]
LOC107982234:WT1/WT1-AS bi-directional promoter region [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

11p13

Genomic location:

Preferred name:

NM_024426.6(WT1):c.391C>T (p.Pro131Ser)

HGVS:

NC_000011.10:g.32434970G>A
NG_009272.1:g.5572C>T
NG_050766.1:g.4223G>A
NM_000378.6:c.391C>T
NM_024424.5:c.391C>T
NM_024426.6:c.391C>TMANE SELECT
NP_000369.4:p.Pro131Ser
NP_077742.3:p.Pro131Ser
NP_077744.4:p.Pro131Ser
LRG_525:g.5572C>T
NC_000011.9:g.32456516G>A
NR_160306.1:n.570C>T

Protein change:

P131S

Links:

dbSNP: rs564706633

NCBI 1000 Genomes Browser:

rs564706633

Molecular consequence:

NM_000378.6:c.391C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024424.5:c.391C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024426.6:c.391C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_160306.1:n.570C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Drash syndrome (DDS)
Synonyms:: WILMS TUMOR AND PSEUDO- OR TRUE HERMAPHRODITISM; Wilms tumor and pseudohermaphroditism; Nephropathy, wilms tumor, and genital anomalies; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008682; MedGen: C0950121; Orphanet: 220; OMIM: 194080

Name:: Frasier syndrome
Identifiers:: MONDO: MONDO:0007635; MeSH: D052159; MedGen: C0950122; Orphanet: 347; OMIM: 136680

Name:: Wilms tumor 1 (WT1)
Synonyms:: Wilms tumor, somatic
Identifiers:: MONDO: MONDO:0008679; MedGen: CN033288; Orphanet: 654; OMIM: 194070

Name:: 11p partial monosomy syndrome (WAGR)
Synonyms:: CHROMOSOME 11p13 DELETION SYNDROME; WAGR syndrome; WAGR Complex; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008681; MedGen: C0206115; Orphanet: 893; OMIM: 194072

Recent activity

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Arabideae trnL-trnF intergenic spacer, partial sequence; chloroplast.
Arabideae trnL-trnF intergenic spacer, partial sequence; chloroplast.
PopSet: 58978678

PopSet
Core Binding Factors
Core Binding Factors
Heterodimeric transcription factors containing a DNA-binding alpha subunits, (CORE BINDING FACTOR ALPHA SUBUNITS), along with a non-DNA-binding beta subunits, CORE BINDING FAC...<br/>Year introduced: 2006(1997)

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002216364	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 26, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26358501, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002216364

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 26, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel WT1 Missense Mutations in Han Chinese Women with Premature Ovarian Failure.

Wang H, Li G, Zhang J, Gao F, Li W, Qin Y, Chen ZJ.

Sci Rep. 2015 Sep 11;5:13983. doi: 10.1038/srep13983.

PubMed [citation]

PMID:: 26358501
PMCID:: PMC4566091

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002216364.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 584764). This missense change has been observed in individual(s) with premature ovarian failure (PMID: 26358501). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces proline with serine at codon 126 of the WT1 protein (p.Pro126Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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