rs151010429
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_024334.3(TMEM43):c.169G>A(p.Ala57Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000669 in 1,613,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A57S) has been classified as Uncertain significance.
Frequency
Consequence
NM_024334.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.169G>A | p.Ala57Thr | missense_variant | 3/12 | ENST00000306077.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.169G>A | p.Ala57Thr | missense_variant | 3/12 | 1 | NM_024334.3 | P1 | |
TMEM43 | ENST00000432444.2 | c.*199G>A | 3_prime_UTR_variant, NMD_transcript_variant | 4/13 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000916 AC: 23AN: 251080Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135668
GnomAD4 exome AF: 0.0000691 AC: 101AN: 1461492Hom.: 0 Cov.: 30 AF XY: 0.0000729 AC XY: 53AN XY: 726992
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74332
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 5 Pathogenic:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2013 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 17, 2020 | Identified in several individuals from an unselected cohort of community health system patients who underwent exome sequencing; none of these individuals were found to carry a diagnosis of ARVC based on electronic health record review (Haggerty et al., 2017); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#88981; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31402444, 28471438, 27153395, 26183555, 23812740) - |
Arrhythmogenic right ventricular cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | - | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 07, 2019 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 23, 2021 | 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