rs35924492
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_024334.3(TMEM43):c.698A>G(p.Tyr233Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00111 in 1,614,180 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. Y233Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_024334.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.698A>G | p.Tyr233Cys | missense_variant | 8/12 | ENST00000306077.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.698A>G | p.Tyr233Cys | missense_variant | 8/12 | 1 | NM_024334.3 | P1 | |
TMEM43 | ENST00000432444.2 | c.*728A>G | 3_prime_UTR_variant, NMD_transcript_variant | 9/13 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00597 AC: 909AN: 152212Hom.: 5 Cov.: 33
GnomAD3 exomes AF: 0.00155 AC: 390AN: 251330Hom.: 3 AF XY: 0.00106 AC XY: 144AN XY: 135836
GnomAD4 exome AF: 0.000601 AC: 879AN: 1461850Hom.: 15 Cov.: 32 AF XY: 0.000523 AC XY: 380AN XY: 727230
GnomAD4 genome ? AF: 0.00598 AC: 911AN: 152330Hom.: 5 Cov.: 33 AF XY: 0.00577 AC XY: 430AN XY: 74482
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 11, 2013 | Tyr233Cys in exon 8 of TMEM43: This variant is not expected to have clinical sig nificance because it has been identified in 2.5% (111/4406) of African American chromosomes from by the NHLBI Exome Sequencing Project (http://evs.gs.washington .edu/EVS/rs35924492). - |
Benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jan 05, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | - | - - |
Cardiomyopathy Benign:3
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 19, 2018 | - - |
Benign, no assertion criteria provided | clinical testing | Cohesion Phenomics | Sep 23, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Oct 26, 2016 | - - |
Arrhythmogenic right ventricular dysplasia 5;C3553060:Emery-Dreifuss muscular dystrophy 7, autosomal dominant;C5676964:Auditory neuropathy, autosomal dominant 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 30, 2021 | - - |
Arrhythmogenic right ventricular dysplasia 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 20, 2015 | This alteration is classified as 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. - |
Sudden cardiac arrest Benign:1
Benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Mar 15, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at