rs193922707
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_024334.3(TMEM43):c.797G>A(p.Arg266Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R266R) has been classified as Benign.
Frequency
Consequence
NM_024334.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.797G>A | p.Arg266Gln | missense_variant | 10/12 | ENST00000306077.5 | NP_077310.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.797G>A | p.Arg266Gln | missense_variant | 10/12 | 1 | NM_024334.3 | ENSP00000303992.5 | ||
ENSG00000268279 | ENST00000608606.1 | n.32G>A | non_coding_transcript_exon_variant | 2/5 | 5 | ENSP00000476275.1 | ||||
TMEM43 | ENST00000432444.2 | n.*827G>A | non_coding_transcript_exon_variant | 11/13 | 3 | ENSP00000395617.1 | ||||
TMEM43 | ENST00000432444.2 | n.*827G>A | 3_prime_UTR_variant | 11/13 | 3 | ENSP00000395617.1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000441 AC: 11AN: 249604Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135060
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461134Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 726868
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74372
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 5;C3553060:Emery-Dreifuss muscular dystrophy 7, autosomal dominant;C5676964:Auditory neuropathy, autosomal dominant 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 02, 2021 | - - |
Arrhythmogenic right ventricular cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing;curation | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 18, 2011 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 09, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Arrhythmogenic right ventricular dysplasia 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 08, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 266 of the TMEM43 protein (p.Arg266Gln). This variant is present in population databases (rs193922707, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. 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: 36872). - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2024 | 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