rs1057524887
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 4P and 3B. PM2PM5BP4_ModerateBP6
The NM_006005.3(WFS1):c.172G>A(p.Ala58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A58V) has been classified as Likely benign.
Frequency
Consequence
NM_006005.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.172G>A | p.Ala58Thr | missense_variant | 2/8 | ENST00000226760.5 | |
WFS1 | NM_001145853.1 | c.172G>A | p.Ala58Thr | missense_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WFS1 | ENST00000226760.5 | c.172G>A | p.Ala58Thr | missense_variant | 2/8 | 1 | NM_006005.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1418826Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 701602
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Type 2 diabetes mellitus;C1833021:Autosomal dominant nonsyndromic hearing loss 6;C3280358:Wolfram-like syndrome;C3805412:Cataract 41;C4551693:Wolfram syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 02, 2021 | - - |
Monogenic diabetes Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Oct 11, 2016 | ACMG Criteria: PM2, PP3, BP4 - |
Wolfram syndrome 1 Benign:1
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 rs1057524887 in Wolfram's syndrome yet. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at