rs201916031
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The ENST00000306077.5(TMEM43):c.705+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000647 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000306077.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.705+7G>A | splice_region_variant, intron_variant | ENST00000306077.5 | NP_077310.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.705+7G>A | splice_region_variant, intron_variant | 1 | NM_024334.3 | ENSP00000303992 | P1 | |||
TMEM43 | ENST00000432444.2 | c.*735+7G>A | splice_region_variant, intron_variant, NMD_transcript_variant | 3 | ENSP00000395617 |
Frequencies
GnomAD3 genomes AF: 0.000473 AC: 72AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000410 AC: 103AN: 251310Hom.: 0 AF XY: 0.000398 AC XY: 54AN XY: 135836
GnomAD4 exome AF: 0.000665 AC: 972AN: 1461784Hom.: 0 Cov.: 32 AF XY: 0.000597 AC XY: 434AN XY: 727192
GnomAD4 genome AF: 0.000473 AC: 72AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000430 AC XY: 32AN XY: 74482
ClinVar
Submissions by phenotype
not provided Benign:6
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 13, 2017 | Variant summary: c.705+7G>A in TMEM43 gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect the normal splicing pattern, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at a frequency of 0.000346 (42/121280 chrs tested), predominantly in individuals of European descent (0.0042; 28/66666 chrs tested). The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant of 0.000025. The variant is present in a control population dataset of gnomAD at a frequency of 0.00038 (106/277038 chrs), further supporting benign outcome. The variant of interest has been reported in at least 2 ARVD individuals in published reports without sufficient evidence to rule in or rule out causality. It is cited as Likely Benign by reputable databases/clinical laboratories. Considering all, the variant was classified as Benign. - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | TMEM43: BP4 - |
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 05, 2015 | c.705+7G>A in intron 8 of TMEM43: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. It has also been identified in 28/66666 European chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201916031). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 02, 2016 | The c.705+7G>A intronic alteration consists of a G to A substitution nucleotides after coding exon 8 in the TMEM43 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Arrhythmogenic right ventricular dysplasia 5;C3553060:Emery-Dreifuss muscular dystrophy 7, autosomal dominant;C5676964:Auditory neuropathy, autosomal dominant 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 13, 2021 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Mar 05, 2018 | - - |
Arrhythmogenic right ventricular dysplasia 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at