chr3-14130938-C-T
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_024334.3(TMEM43):c.279C>T(p.Gly93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000825 in 1,611,828 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 1 hom. )
Consequence
TMEM43
NM_024334.3 synonymous
NM_024334.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.404
Genes affected
TMEM43 (HGNC:28472): (transmembrane protein 43) This gene belongs to the TMEM43 family. Defects in this gene are the cause of familial arrhythmogenic right ventricular dysplasia type 5 (ARVD5), also known as arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5). Arrhythmogenic right ventricular dysplasia is an inherited disorder, often involving both ventricles, and is characterized by ventricular tachycardia, heart failure, sudden cardiac death, and fibrofatty replacement of cardiomyocytes. This gene contains a response element for PPAR gamma (an adipogenic transcription factor), which may explain the fibrofatty replacement of the myocardium, a characteristic pathological finding in ARVC. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 3-14130938-C-T is Benign according to our data. Variant chr3-14130938-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 343504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.404 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000414 (63/152294) while in subpopulation AFR AF= 0.00147 (61/41560). AF 95% confidence interval is 0.00117. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 63 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.279C>T | p.Gly93= | synonymous_variant | 3/12 | ENST00000306077.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.279C>T | p.Gly93= | synonymous_variant | 3/12 | 1 | NM_024334.3 | P1 | |
TMEM43 | ENST00000432444.2 | c.*309C>T | 3_prime_UTR_variant, NMD_transcript_variant | 4/13 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000414 AC: 63AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000112 AC: 28AN: 249178Hom.: 1 AF XY: 0.000104 AC XY: 14AN XY: 134680
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GnomAD4 exome AF: 0.0000480 AC: 70AN: 1459534Hom.: 1 Cov.: 31 AF XY: 0.0000469 AC XY: 34AN XY: 725626
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GnomAD4 genome AF: 0.000414 AC: 63AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74464
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 28, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 01, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 13, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 07, 2021 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 25, 2018 | - - |
TMEM43-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 11, 2023 | 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). - |
Arrhythmogenic right ventricular dysplasia 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 13, 2017 | 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at