chr11-32435274-G-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_024426.6(WT1):c.87C>A(p.Cys29*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. C29C) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
WT1
NM_024426.6 stop_gained
NM_024426.6 stop_gained
Scores
2
2
2
Clinical Significance
Conservation
PhyloP100: 0.433
Publications
0 publications found
Genes affected
WT1 (HGNC:12796): (WT1 transcription factor) This gene encodes a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilms tumor. This gene exhibits complex tissue-specific and polymorphic imprinting pattern, with biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues. Multiple transcript variants have been described. In several variants, there is evidence for the use of a non-AUG (CUG) translation initiation codon upstream of, and in-frame with the first AUG. Authors of PMID:7926762 also provide evidence that WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated. [provided by RefSeq, Mar 2015]
WT1-AS (HGNC:18135): (WT1 antisense RNA) This gene is located upstream of the Wilms tumor 1 (WT1) gene; these two genes are bi-directionally transcribed from the same promoter region. This gene is imprinted in kidney, with preferential expression from the paternal allele. Imprinting defects at chromosome 11p13 may contribute to tumorigenesis. [provided by RefSeq, May 2014]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 138 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_024426.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| WT1 | TSL:1 MANE Select | c.87C>A | p.Cys29* | stop_gained | Exon 1 of 10 | ENSP00000415516.5 | P19544-7 | ||
| WT1 | TSL:1 | c.87C>A | p.Cys29* | stop_gained | Exon 1 of 9 | ENSP00000492269.3 | P19544-8 | ||
| WT1 | TSL:1 | c.87C>A | p.Cys29* | stop_gained | Exon 1 of 9 | ENSP00000331327.5 | J3KNN9 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1382496Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0AN XY: 682172
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1382496
Hom.:
Cov.:
44
AF XY:
AC XY:
0
AN XY:
682172
African (AFR)
AF:
AC:
0
AN:
31598
American (AMR)
AF:
AC:
0
AN:
35800
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25158
East Asian (EAS)
AF:
AC:
0
AN:
35838
South Asian (SAS)
AF:
AC:
0
AN:
79210
European-Finnish (FIN)
AF:
AC:
0
AN:
33486
Middle Eastern (MID)
AF:
AC:
0
AN:
4694
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1078934
Other (OTH)
AF:
AC:
0
AN:
57778
GnomAD4 genome
GnomAD4 genome
Cov.:
30
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
11p partial monosomy syndrome;C0950121:Drash syndrome;C0950122:Frasier syndrome;CN033288:Wilms tumor 1 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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