chr5-131159551-C-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_005340.7(HINT1):c.277G>T(p.Gly93Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,613,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G93V) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005340.7 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HINT1 | NM_005340.7 | c.277G>T | p.Gly93Cys | missense_variant | 3/3 | ENST00000304043.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HINT1 | ENST00000304043.10 | c.277G>T | p.Gly93Cys | missense_variant | 3/3 | 1 | NM_005340.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151994Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251340Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135836
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461706Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727184
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151994Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74236
ClinVar
Submissions by phenotype
Autosomal recessive axonal neuropathy with neuromyotonia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 20, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 93 of the HINT1 protein (p.Gly93Cys). This variant is present in population databases (rs755979803, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HINT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 568648). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at