chr4-6301538-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_006005.3(WFS1):c.1743C>T(p.Gly581Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,613,992 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006005.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.1743C>T | p.Gly581Gly | synonymous_variant | Exon 8 of 8 | ENST00000226760.5 | NP_005996.2 | |
WFS1 | NM_001145853.1 | c.1743C>T | p.Gly581Gly | synonymous_variant | Exon 8 of 8 | NP_001139325.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152224Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000103 AC: 26AN: 251336Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135880
GnomAD4 exome AF: 0.0000746 AC: 109AN: 1461650Hom.: 0 Cov.: 100 AF XY: 0.0000646 AC XY: 47AN XY: 727142
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152342Hom.: 0 Cov.: 34 AF XY: 0.0000537 AC XY: 4AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
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WFS1: BP4, BP7 -
not specified Benign:1
Gly581Gly in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1/7020 European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS). -
Wolfram syndrome 1 Benign:1
Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy.However no sufficient evidence is found to ascertain the role of this particular variant rs377539343 in Wolfram's syndrome yet. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at