rs372452104
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The ENST00000379802.8(DSP):āc.5123C>Gā(p.Ser1708Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1708F) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000379802.8 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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.5123C>G | p.Ser1708Cys | missense_variant | 23/24 | ENST00000379802.8 | NP_004406.2 | |
DSP | NM_001008844.3 | c.3583-1329C>G | intron_variant | NP_001008844.1 | ||||
DSP | NM_001319034.2 | c.4050+1073C>G | intron_variant | NP_001305963.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.5123C>G | p.Ser1708Cys | missense_variant | 23/24 | 1 | NM_004415.4 | ENSP00000369129 | P2 | |
DSP | ENST00000418664.2 | c.3583-1329C>G | intron_variant | 1 | ENSP00000396591 | A2 | ||||
DSP | ENST00000710359.1 | c.4050+1073C>G | intron_variant | ENSP00000518230 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461848Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727232
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74378
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 18, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 578928). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1708 of the DSP protein (p.Ser1708Cys). - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2023 | The p.S1708C variant (also known as c.5123C>G), located in coding exon 23 of the DSP gene, results from a C to G substitution at nucleotide position 5123. The serine at codon 1708 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at