19-54162245-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_144686.4(TMC4):c.1543G>A(p.Ala515Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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
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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.1543G>A | p.Ala515Thr | missense_variant | Exon 11 of 15 | ENST00000619895.5 | NP_653287.2 | |
TMC4 | NM_001145303.3 | c.1561G>A | p.Ala521Thr | missense_variant | Exon 11 of 15 | NP_001138775.2 | ||
TMC4 | XM_011526486.3 | c.1081G>A | p.Ala361Thr | missense_variant | Exon 8 of 12 | XP_011524788.1 | ||
TMC4 | XR_935741.3 | n.1604G>A | non_coding_transcript_exon_variant | Exon 11 of 15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMC4 | ENST00000619895.5 | c.1543G>A | p.Ala515Thr | missense_variant | Exon 11 of 15 | 1 | NM_144686.4 | ENSP00000479458.1 | ||
TMC4 | ENST00000617472.4 | c.1561G>A | p.Ala521Thr | missense_variant | Exon 11 of 15 | 1 | ENSP00000477627.1 | |||
TMC4 | ENST00000613723.4 | n.784G>A | non_coding_transcript_exon_variant | Exon 5 of 9 | 1 | |||||
TMC4 | ENST00000495398.1 | n.374G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 27
GnomAD4 exome Cov.: 38
GnomAD4 genome Cov.: 27
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1561G>A (p.A521T) alteration is located in exon 11 (coding exon 11) of the TMC4 gene. This alteration results from a G to A substitution at nucleotide position 1561, causing the alanine (A) at amino acid position 521 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
Publications
No publications associated with this variant yet.