rs948132360
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_024426.6(WT1):c.26C>T(p.Pro9Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000261 in 1,532,140 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P9A) has been classified as Uncertain significance.
Frequency
Consequence
NM_024426.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WT1 | NM_024426.6 | c.26C>T | p.Pro9Leu | missense_variant | 1/10 | ENST00000452863.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WT1 | ENST00000452863.10 | c.26C>T | p.Pro9Leu | missense_variant | 1/10 | 1 | NM_024426.6 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151490Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000774 AC: 1AN: 129126Hom.: 0 AF XY: 0.0000142 AC XY: 1AN XY: 70626
GnomAD4 exome AF: 0.00000217 AC: 3AN: 1380650Hom.: 0 Cov.: 44 AF XY: 0.00000147 AC XY: 1AN XY: 681142
GnomAD4 genome ? AF: 0.00000660 AC: 1AN: 151490Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74030
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 | Nov 08, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 4 of the WT1 protein (p.Pro4Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with WT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 864517). 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 tolerated. 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. - |
11p partial monosomy syndrome;C0344542:Aniridia 1;C0345967:Mesothelioma, malignant;C0950121:Drash syndrome;C0950122:Frasier syndrome;C1837026:Meacham syndrome;C3151568:Nephrotic syndrome, type 4;CN033288:Wilms tumor 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 04, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 19, 2022 | The WT1 c.26C>T; p.Pro9Leu variant (rs948132360), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 864517). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The proline at codon 9 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.091). Due to limited information, the clinical significance of this variant is uncertain at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at