11-32388003-AACACACACACACACACACAC-AACAC

Variant names:

• chr11-32388003-AACACACACACACACAC-A
• rs58549495
• NM_024426.6:c.*1039_*1054delGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_024426.6(WT1):​c.*1039_*1054delGTGTGTGTGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 229,208 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: WT1 NM_024426.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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 Likely_benign. Variant got -1 ACMG points.

• BS2: High AC in GnomAd4 at 21 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6	c.*1039_*1054delGTGTGTGTGTGTGTGT		3_prime_UTR_variant	Exon 10 of 10	ENST00000452863.10	NP_077744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863	c.*1039_*1054delGTGTGTGTGTGTGTGT		3_prime_UTR_variant	Exon 10 of 10	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes AF: 0.000143 AC: 21 AN: 146470 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000499

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000681

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00301

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000303

Gnomad OTH AF: 0.000498

GnomAD4 exome AF: 0.000182 AC: 15 AN: 82622 Hom.: 0 AF XY: 0.000105 AC XY: 4 AN XY: 38146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00122

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000197

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000143 AC: 21 AN: 146586 Hom.: 0 Cov.: 0 AF XY: 0.000168 AC XY: 12 AN XY: 71296

Gnomad4 AFR AF: 0.0000497

Gnomad4 AMR AF: 0.0000680

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00302

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000303

Gnomad4 OTH AF: 0.000493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58549495; hg19: chr11-32409549;