rs201477740
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_152468.5(TMC8):c.1577G>A(p.Arg526His) variant causes a missense change. The variant allele was found at a frequency of 0.000154 in 1,612,006 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R526C) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC8 | NM_152468.5 | c.1577G>A | p.Arg526His | missense_variant | 13/16 | ENST00000318430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC8 | ENST00000318430.10 | c.1577G>A | p.Arg526His | missense_variant | 13/16 | 1 | NM_152468.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000336 AC: 84AN: 249902Hom.: 0 AF XY: 0.000273 AC XY: 37AN XY: 135294
GnomAD4 exome AF: 0.000154 AC: 225AN: 1459828Hom.: 3 Cov.: 33 AF XY: 0.000156 AC XY: 113AN XY: 726312
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74348
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2022 | The c.1577G>A (p.R526H) alteration is located in exon 13 (coding exon 12) of the TMC8 gene. This alteration results from a G to A substitution at nucleotide position 1577, causing the arginine (R) at amino acid position 526 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
TMC8-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 11, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Epidermodysplasia verruciformis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at