rs141675061
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_024334.3(TMEM43):c.1095G>A(p.Ala365Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_024334.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.1095G>A | p.Ala365Ala | synonymous_variant | Exon 12 of 12 | ENST00000306077.5 | NP_077310.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.1095G>A | p.Ala365Ala | synonymous_variant | Exon 12 of 12 | 1 | NM_024334.3 | ENSP00000303992.5 | ||
ENSG00000268279 | ENST00000608606.1 | n.235+2390G>A | intron_variant | Intron 3 of 4 | 5 | ENSP00000476275.1 |
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000175 AC: 44AN: 251404Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135886
GnomAD4 exome AF: 0.000397 AC: 580AN: 1461866Hom.: 0 Cov.: 32 AF XY: 0.000397 AC XY: 289AN XY: 727232
GnomAD4 genome AF: 0.000197 AC: 30AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74342
ClinVar
Submissions by phenotype
not specified Benign:2
Ala365Ala in exon 12 of TMEM43: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in (4/8600) European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washin gton.edu/EVS/; dbSNP rs141675061). Ala365Ala in exon 12 of TMEM43 (rs141675061 ; allele frequency = 4/8600) ** -
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Arrhythmogenic right ventricular dysplasia 5 Benign:2
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Cardiomyopathy Benign:1
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TMEM43-related disorder Benign:1
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). -
not provided Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at