5-131159497-C-CGT
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_005340.7(HINT1):c.330_331insAC(p.Val111ThrfsTer32) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. H110H) has been classified as Likely benign.
Frequency
Consequence
NM_005340.7 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HINT1 | NM_005340.7 | c.330_331insAC | p.Val111ThrfsTer32 | frameshift_variant | 3/3 | ENST00000304043.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HINT1 | ENST00000304043.10 | c.330_331insAC | p.Val111ThrfsTer32 | frameshift_variant | 3/3 | 1 | NM_005340.7 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251438Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461214Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726920
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive axonal neuropathy with neuromyotonia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the HINT1 protein in which other variant(s) (p.His112Asn) have been determined to be pathogenic (PMID: 16835243, 22961002, 31088288). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 659256). This variant has not been reported in the literature in individuals affected with HINT1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change results in a frameshift in the HINT1 gene (p.Val111Thrfs*32). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the HINT1 protein and extend the protein by 15 additional amino acid residues. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at