chr17-78131623-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_152468.5(TMC8):c.35C>T(p.Ala12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 1,551,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. A12T) has been classified as Uncertain significance.
Frequency
Consequence
NM_152468.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC8 | NM_152468.5 | c.35C>T | p.Ala12Val | missense_variant | 2/16 | ENST00000318430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC8 | ENST00000318430.10 | c.35C>T | p.Ala12Val | missense_variant | 2/16 | 1 | NM_152468.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152232Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000155 AC: 23AN: 148822Hom.: 0 AF XY: 0.000112 AC XY: 9AN XY: 80226
GnomAD4 exome AF: 0.0000214 AC: 30AN: 1399088Hom.: 0 Cov.: 31 AF XY: 0.0000217 AC XY: 15AN XY: 690486
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152232Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4AN XY: 74370
ClinVar
Submissions by phenotype
Epidermodysplasia verruciformis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 24, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 12 of the TMC8 protein (p.Ala12Val). This variant is present in population databases (rs748499539, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with TMC8-related conditions. ClinVar contains an entry for this variant (Variation ID: 526242). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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