chr19-54164496-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_144686.4(TMC4):c.1051G>A(p.Ala351Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,948 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 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 Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMC4 | NM_144686.4 | c.1051G>A | p.Ala351Thr | missense_variant | Exon 7 of 15 | ENST00000619895.5 | NP_653287.2 | |
TMC4 | NM_001145303.3 | c.1069G>A | p.Ala357Thr | missense_variant | Exon 7 of 15 | NP_001138775.2 | ||
TMC4 | XM_011526486.3 | c.816-1337G>A | intron_variant | Intron 5 of 11 | XP_011524788.1 | |||
TMC4 | XR_935741.3 | n.1112G>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.1051G>A | p.Ala351Thr | missense_variant | Exon 7 of 15 | 1 | NM_144686.4 | ENSP00000479458.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250046Hom.: 1 AF XY: 0.00000739 AC XY: 1AN XY: 135292
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461730Hom.: 1 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727178
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74420
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1069G>A (p.A357T) 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 1069, causing the alanine (A) at amino acid position 357 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