NM_006005.3:c.825G>A
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4BP6_Very_StrongBP7
The NM_006005.3(WFS1):c.825G>A(p.Ala275Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,612,540 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 Likely benign (★★).
Frequency
Consequence
NM_006005.3 synonymous
Scores
Clinical Significance
Conservation
Publications
- Wolfram-like syndromeInheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics, ClinGen, Orphanet
- Wolfram syndromeInheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- autosomal dominant nonsyndromic hearing loss 6Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- cataract 41Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Wolfram syndrome 1Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
- autosomal dominant nonsyndromic hearing lossInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- early-onset nuclear cataractInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- type 2 diabetes mellitusInheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.825G>A | p.Ala275Ala | synonymous_variant | Exon 7 of 8 | ENST00000226760.5 | NP_005996.2 | |
WFS1 | NM_001145853.1 | c.825G>A | p.Ala275Ala | synonymous_variant | Exon 7 of 8 | NP_001139325.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152200Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.000116 AC: 29AN: 250364 AF XY: 0.000133 show subpopulations
GnomAD4 exome AF: 0.0000979 AC: 143AN: 1460222Hom.: 0 Cov.: 31 AF XY: 0.0000936 AC XY: 68AN XY: 726440 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000151 AC: 23AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74480 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:3
- -
- -
- -
not specified Benign:2
p.Ala275Ala in exon 7 of WSF1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Type 2 diabetes mellitus;C1833021:Autosomal dominant nonsyndromic hearing loss 6;C3280358:Wolfram-like syndrome;C3805412:Cataract 41;C4551693:Wolfram syndrome 1 Benign:1
- -
WFS1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
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 rs566634291 in Wolfram's syndrome yet. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at