NM_024426.6(WT1):c.973G>A (p.Ala325Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 1, 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:: RCV001856410.5

Allele description [Variation Report for NM_024426.6(WT1):c.973G>A (p.Ala325Thr)]

NM_024426.6(WT1):c.973G>A (p.Ala325Thr)

Gene:

WT1:WT1 transcription factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p13

Genomic location:

Preferred name:

NM_024426.6(WT1):c.973G>A (p.Ala325Thr)

HGVS:

NC_000011.10:g.32416533C>T
NG_009272.1:g.24009G>A
NM_000378.6:c.965+1044G>A
NM_001198551.2:c.322G>A
NM_001198552.2:c.314+1044G>A
NM_001407044.1:c.973G>A
NM_001407046.1:c.973G>A
NM_001407047.1:c.850G>A
NM_001407051.1:c.211G>A
NM_024424.5:c.973G>A
NM_024426.6:c.973G>AMANE SELECT
NP_001185480.1:p.Ala108Thr
NP_001185480.1:p.Ala108Thr
NP_001393973.1:p.Ala325Thr
NP_001393975.1:p.Ala325Thr
NP_001393976.1:p.Ala284Thr
NP_001393980.1:p.Ala71Thr
NP_077742.3:p.Ala325Thr
NP_077744.3:p.Ala320Thr
NP_077744.4:p.Ala325Thr
LRG_525t1:c.958G>A
LRG_525t2:c.322G>A
LRG_525:g.24009G>A
LRG_525p1:p.Ala320Thr
LRG_525p2:p.Ala108Thr
NC_000011.9:g.32438079C>T
NC_000011.9:g.32438079C>T
NM_001198551.1:c.322G>A
NM_024426.3:c.958G>A
NM_024426.4:c.958G>A
NR_160306.1:n.1305G>A

Protein change:

A108T

Links:

dbSNP: rs1712081462

NCBI 1000 Genomes Browser:

rs1712081462

Molecular consequence:

NM_000378.6:c.965+1044G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001198552.2:c.314+1044G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001198551.2:c.322G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407044.1:c.973G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407046.1:c.973G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407047.1:c.850G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407051.1:c.211G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024424.5:c.973G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024426.6:c.973G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_160306.1:n.1305G>A - 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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Arabidopsis thaliana plant adhesion molecule 1 (PAM1), mRNA
Arabidopsis thaliana plant adhesion molecule 1 (PAM1), mRNA
gi|186523240|ref|NM_121598.4|

Nucleotide
ATP-binding protein [Arthrobacter humicola]
ATP-binding protein [Arthrobacter humicola]
gi|2730099423|ref|WP_344363135.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002314775	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002314775

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 1, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV002314775.3

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

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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 878161). This variant has not been reported in the literature in individuals affected with WT1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 320 of the WT1 protein (p.Ala320Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine.

#	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: Sep 29, 2024

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Relating variation to medicine