rs377585035
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_024334.3(TMEM43):c.864C>T(p.His288=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,614,048 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
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
TMEM43
NM_024334.3 synonymous
NM_024334.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.72
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
Variant 3-14135890-C-T is Benign according to our data. Variant chr3-14135890-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 519458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-14135890-C-T is described in Lovd as [Likely_benign]. Variant chr3-14135890-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.72 with no splicing effect.
BS2
?
High AC in GnomAd4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.864C>T | p.His288= | synonymous_variant | 10/12 | ENST00000306077.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.864C>T | p.His288= | synonymous_variant | 10/12 | 1 | NM_024334.3 | P1 | |
TMEM43 | ENST00000432444.2 | c.*894C>T | 3_prime_UTR_variant, NMD_transcript_variant | 11/13 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152248Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000519 AC: 13AN: 250320Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135376
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GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461800Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 727206
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GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74382
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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
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 23, 2019 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2021 | See Variant Classification Assertion Criteria. - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Arrhythmogenic right ventricular dysplasia 5 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 18, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 22, 2018 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 02, 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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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at