NM_024426.6:c.203G>C

Variant names:

• chr11-32435158-C-G
• NM_024426.6:c.203G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024426.6(WT1):​c.203G>C​(p.Gly68Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,369,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: WT1 NM_024426.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086301416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6	c.203G>C	p.Gly68Ala	missense_variant	Exon 1 of 10	ENST00000452863.10	NP_077744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863.10	c.203G>C	p.Gly68Ala	missense_variant	Exon 1 of 10	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1369660 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 674798

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.32e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.55
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.47	N
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.086	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.020	N;N;N;.;.;.
REVEL	Benign	0.030
Sift	Benign	0.14	T;T;T;.;.;.
Sift4G	Pathogenic	0.0	D;D;T;.;.;.
Vest4		0.092
MutPred		0.075		Loss of glycosylation at S62 (P = 0.0714);Loss of glycosylation at S62 (P = 0.0714);Loss of glycosylation at S62 (P = 0.0714);Loss of glycosylation at S62 (P = 0.0714);Loss of glycosylation at S62 (P = 0.0714);Loss of glycosylation at S62 (P = 0.0714);
MVP		0.014
ClinPred		0.054	T
GERP RS		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-32456704;