rs201658872
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_144686.4(TMC4):c.1006G>A(p.Ala336Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_144686.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMC4 | NM_144686.4 | c.1006G>A | p.Ala336Thr | missense_variant | Exon 7 of 15 | ENST00000619895.5 | NP_653287.2 | |
TMC4 | NM_001145303.3 | c.1024G>A | p.Ala342Thr | missense_variant | Exon 7 of 15 | NP_001138775.2 | ||
TMC4 | XM_011526486.3 | c.816-1382G>A | intron_variant | Intron 5 of 11 | XP_011524788.1 | |||
TMC4 | XR_935741.3 | n.1067G>A | non_coding_transcript_exon_variant | Exon 7 of 15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMC4 | ENST00000619895.5 | c.1006G>A | p.Ala336Thr | missense_variant | Exon 7 of 15 | 1 | NM_144686.4 | ENSP00000479458.1 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152164Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000288 AC: 72AN: 249942Hom.: 0 AF XY: 0.000303 AC XY: 41AN XY: 135292
GnomAD4 exome AF: 0.000194 AC: 283AN: 1461674Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 156AN XY: 727160
GnomAD4 genome AF: 0.000210 AC: 32AN: 152164Hom.: 0 Cov.: 31 AF XY: 0.000229 AC XY: 17AN XY: 74336
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1024G>A (p.A342T) alteration is located in exon 7 (coding exon 7) of the TMC4 gene. This alteration results from a G to A substitution at nucleotide position 1024, causing the alanine (A) at amino acid position 342 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at