chr3-14131678-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_024334.3(TMEM43):c.392+4A>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000959 in 1,459,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_024334.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.392+4A>G | splice_region_variant, intron_variant | Intron 4 of 11 | ENST00000306077.5 | NP_077310.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.392+4A>G | splice_region_variant, intron_variant | Intron 4 of 11 | 1 | NM_024334.3 | ENSP00000303992.5 | |||
TMEM43 | ENST00000432444.2 | n.*422+4A>G | splice_region_variant, intron_variant | Intron 5 of 12 | 3 | ENSP00000395617.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1459236Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8AN XY: 726092
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
The 392+4A>G variant in TMEM43 has not been reported in the literature nor previ ously identified by our laboratory. It has also not been detected in 2 large and broad populations (European and African American) screened by the NHLBI Exome S equencing Project (http://evs.gs.washington.edu/EVS), which is consistent with a role in disease. This variant is located in the 5' splice region and computatio nal tools do suggest a slight impact to splicing (please note that their accurac y is unknown). Additional information is needed to fully assess the clinical sig nificance of this variant. -
Arrhythmogenic right ventricular dysplasia 5 Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 46144). This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 4 of the TMEM43 gene. It does not directly change the encoded amino acid sequence of the TMEM43 protein. It affects a nucleotide within the consensus splice site. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at