rs373631928
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001127198.5(TMC6):c.554C>T(p.Pro185Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000602 in 1,593,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P185P) has been classified as Likely benign.
Frequency
Consequence
NM_001127198.5 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 |
---|---|---|---|---|---|---|---|
TMC6 | NM_001127198.5 | c.554C>T | p.Pro185Leu | missense_variant | 7/20 | ENST00000590602.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC6 | ENST00000590602.6 | c.554C>T | p.Pro185Leu | missense_variant | 7/20 | 2 | NM_001127198.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152226Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000865 AC: 18AN: 208172Hom.: 0 AF XY: 0.0000787 AC XY: 9AN XY: 114322
GnomAD4 exome AF: 0.0000333 AC: 48AN: 1441104Hom.: 0 Cov.: 34 AF XY: 0.0000279 AC XY: 20AN XY: 715732
GnomAD4 genome ? AF: 0.000315 AC: 48AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29AN XY: 74496
ClinVar
Submissions by phenotype
Epidermodysplasia verruciformis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 185 of the TMC6 protein (p.Pro185Leu). This variant is present in population databases (rs373631928, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with TMC6-related conditions. ClinVar contains an entry for this variant (Variation ID: 526240). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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