22-23766188-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_213720.3(CHCHD10):c.349A>T(p.Ser117Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,438 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S117N) has been classified as Uncertain significance.
Frequency
Consequence
NM_213720.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHCHD10 | NM_213720.3 | c.349A>T | p.Ser117Cys | missense_variant | 3/4 | ENST00000484558.3 | |
CHCHD10 | NM_001301339.2 | c.370A>T | p.Ser124Cys | missense_variant | 3/4 | ||
CHCHD10 | NR_125755.2 | n.394A>T | non_coding_transcript_exon_variant | 3/4 | |||
CHCHD10 | NR_125756.2 | n.227A>T | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHCHD10 | ENST00000484558.3 | c.349A>T | p.Ser117Cys | missense_variant | 3/4 | 1 | NM_213720.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460438Hom.: 0 Cov.: 65 AF XY: 0.00000275 AC XY: 2AN XY: 726418
GnomAD4 genome Cov.: 30
ClinVar
Submissions by phenotype
Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Oct 20, 2021 | _x000D_ Criteria applied: PS4_SUP, PM2_SUP, PP3 - |
Lower motor neuron syndrome with late-adult onset;C4014648:Frontotemporal dementia and/or amyotrophic lateral sclerosis 2;C4015513:Autosomal dominant mitochondrial myopathy with exercise intolerance Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 24, 2019 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with CHCHD10-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with cysteine at codon 117 of the CHCHD10 protein (p.Ser117Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at