6-7580212-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004415.4(DSP):c.4022G>T(p.Arg1341Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004415.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.4022G>T | p.Arg1341Leu | missense_variant | Exon 23 of 24 | ENST00000379802.8 | NP_004406.2 | |
DSP | NM_001319034.2 | c.4022G>T | p.Arg1341Leu | missense_variant | Exon 23 of 24 | NP_001305963.1 | ||
DSP | NM_001008844.3 | c.3582+440G>T | intron_variant | Intron 23 of 23 | NP_001008844.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.4022G>T | p.Arg1341Leu | missense_variant | Exon 23 of 24 | 1 | NM_004415.4 | ENSP00000369129.3 | ||
DSP | ENST00000418664.2 | c.3582+440G>T | intron_variant | Intron 23 of 23 | 1 | ENSP00000396591.2 | ||||
DSP | ENST00000710359.1 | c.4022G>T | p.Arg1341Leu | missense_variant | Exon 23 of 24 | ENSP00000518230.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461838Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727214
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Uncertain:1
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Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Uncertain:1
This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1341 of the DSP protein (p.Arg1341Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 2775303). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -
Cardiomyopathy Uncertain:1
This missense variant replaces arginine with leucine at codon 1341 of the DSP protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at