NM_024426.6:c.1154G>A
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4BP6BS2_Supporting
The NM_024426.6(WT1):c.1154G>A(p.Arg385Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000458 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R385W) has been classified as Uncertain significance.
Frequency
Consequence
NM_024426.6 missense
Scores
Clinical Significance
Conservation
Publications
- Denys-Drash syndromeInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, G2P
- Wilms tumor 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
- familial idiopathic steroid-resistant nephrotic syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Frasier syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Likely_benign. The variant received -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WT1 | ENST00000452863.10 | c.1154G>A | p.Arg385Gln | missense_variant | Exon 7 of 10 | 1 | NM_024426.6 | ENSP00000415516.5 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152104Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000278 AC: 7AN: 251392 AF XY: 0.0000294 show subpopulations
GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461858Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 727234 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74422 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Uncertain:1Other:1
- -
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 individual who did not have WT; ExAC: 5/8646 East Asian -
11p partial monosomy syndrome;C0950121:Drash syndrome;C0950122:Frasier syndrome;CN033288:Wilms tumor 1 Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 380 of the WT1 protein (p.Arg380Gln). This variant is present in population databases (rs147241955, gnomAD 0.04%). This missense change has been observed in individual(s) with end-stage renal failure (PMID: 10603123). This variant is also known as c.953G>A (p.Arg312Gln). ClinVar contains an entry for this variant (Variation ID: 135455). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Mesothelioma, malignant;C0950121:Drash syndrome;C0950122:Frasier syndrome;C1837026:Meacham syndrome;C3151568:Nephrotic syndrome, type 4;CN033288:Wilms tumor 1 Uncertain:1
- -
Drash syndrome Uncertain:1
- -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Meacham syndrome Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
Nephrotic syndrome, type 4 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Wilms tumor 1 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at