11-32434777-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024426.6(WT1):c.584C>T(p.Ser195Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,320 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S195C) has been classified as Uncertain significance.
Frequency
Consequence
NM_024426.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WT1 | NM_024426.6 | c.584C>T | p.Ser195Phe | missense_variant | 1/10 | ENST00000452863.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WT1 | ENST00000452863.10 | c.584C>T | p.Ser195Phe | missense_variant | 1/10 | 1 | NM_024426.6 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460320Hom.: 0 Cov.: 41 AF XY: 0.00000138 AC XY: 1AN XY: 726486
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
11p partial monosomy syndrome;C0950121:Drash syndrome;C0950122:Frasier syndrome;CN033288:Wilms tumor 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2021 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with WT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, a(n) neutral and polar amino acid, with phenylalanine, a(n) neutral and non-polar amino acid, at codon 190 of the WT1 protein (p.Ser190Phe). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at