chr3-14141711-CCT-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PVS1_ModerateBP6BS2
The NM_024334.3(TMEM43):c.1120_1121delCT(p.Leu374ValfsTer49) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000502 in 1,614,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024334.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.1120_1121delCT | p.Leu374ValfsTer49 | frameshift_variant | Exon 12 of 12 | ENST00000306077.5 | NP_077310.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.1120_1121delCT | p.Leu374ValfsTer49 | frameshift_variant | Exon 12 of 12 | 1 | NM_024334.3 | ENSP00000303992.5 | ||
ENSG00000268279 | ENST00000608606.1 | n.235+2415_235+2416delCT | intron_variant | Intron 3 of 4 | 5 | ENSP00000476275.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000239 AC: 60AN: 251428Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135904
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461872Hom.: 0 AF XY: 0.0000468 AC XY: 34AN XY: 727234
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74506
ClinVar
Submissions by phenotype
not specified Uncertain:2Benign:1
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: High ExAC freq. No LoF variants in HGMD -
Variant summary: TMEM43 c.1120_1121delCT (p.Leu374ValfsX49) causes a frameshift which results in an extension of the protein. The variant allele was found at a frequency of 0.00024 in 251428 control chromosomes, predominantly at a frequency of 0.0016 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 192-fold of the estimated maximal expected allele frequency for a pathogenic variant in TMEM43 causing Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy phenotype (8.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. c.1120_1121delCT has been reported in the literature as a secondary finding in individual(s) undergoing genetic testing for noncardiac reasons (Abicht_2021). This report does not provide unequivocal conclusions about association of the variant with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely benign and three ClinVar submitters (evaluation after 2014) cite it as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. -
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not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; Frameshift variant predicted to result in protein extension as the last 27 amino acids are lost and replaced with 48 incorrect amino acids; This variant is associated with the following publications: (PMID: 33968641) -
Cardiomyopathy Benign:1
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Arrhythmogenic right ventricular dysplasia 5 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at