rs397517195
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_006005.3(WFS1):c.143C>T(p.Ala48Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000762 in 1,575,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006005.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.143C>T | p.Ala48Val | missense_variant | 2/8 | ENST00000226760.5 | |
WFS1 | NM_001145853.1 | c.143C>T | p.Ala48Val | missense_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WFS1 | ENST00000226760.5 | c.143C>T | p.Ala48Val | missense_variant | 2/8 | 1 | NM_006005.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152260Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000110 AC: 2AN: 181218Hom.: 0 AF XY: 0.0000205 AC XY: 2AN XY: 97508
GnomAD4 exome AF: 0.00000703 AC: 10AN: 1423060Hom.: 0 Cov.: 33 AF XY: 0.0000114 AC XY: 8AN XY: 704086
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152260Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74388
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 20, 2012 | Ala48Val in exon 2 of WFS1: This variant is not expected to have clinical signif icance due to a lack of conservation across species at both the nucleotide and a mino acid level. Of note, rabbit, dolphin, cow, and horse have a valine (Val) a t this position. Therefore, this variant is likely benign. - |
Wolfram syndrome 1 Benign:1
Likely benign, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | 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 rs397517195 in Wolfram's syndrome yet. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at