3-14141704-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_024334.3(TMEM43):āc.1112A>Cā(p.Tyr371Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y371C) has been classified as Uncertain significance.
Frequency
Consequence
NM_024334.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.1112A>C | p.Tyr371Ser | missense_variant | 12/12 | ENST00000306077.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.1112A>C | p.Tyr371Ser | missense_variant | 12/12 | 1 | NM_024334.3 | P1 | |
TMEM43 | ENST00000432444.2 | c.*1142A>C | 3_prime_UTR_variant, NMD_transcript_variant | 13/13 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152030Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251392Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135890
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461840Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727222
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152030Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74256
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 21, 2018 | The p.Y371S variant (also known as c.1112A>C), located in coding exon 12 of the TMEM43 gene, results from an A to C substitution at nucleotide position 1112. The tyrosine at codon 371 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Arrhythmogenic right ventricular dysplasia 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TMEM43 protein function. ClinVar contains an entry for this variant (Variation ID: 1053420). This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. This variant is present in population databases (rs752269639, gnomAD 0.01%). This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 371 of the TMEM43 protein (p.Tyr371Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at