rs1554106853
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000379802.8(DSP):āc.1382T>Cā(p.Ile461Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. I461I) has been classified as Likely benign.
Frequency
Consequence
ENST00000379802.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.1382T>C | p.Ile461Thr | missense_variant | 11/24 | ENST00000379802.8 | NP_004406.2 | |
DSP | NM_001319034.2 | c.1382T>C | p.Ile461Thr | missense_variant | 11/24 | NP_001305963.1 | ||
DSP | NM_001008844.3 | c.1382T>C | p.Ile461Thr | missense_variant | 11/24 | NP_001008844.1 | ||
DSP | NM_001406591.1 | c.1382T>C | p.Ile461Thr | missense_variant | 11/11 | NP_001393520.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.1382T>C | p.Ile461Thr | missense_variant | 11/24 | 1 | NM_004415.4 | ENSP00000369129 | P2 | |
DSP | ENST00000418664.2 | c.1382T>C | p.Ile461Thr | missense_variant | 11/24 | 1 | ENSP00000396591 | A2 | ||
DSP | ENST00000710359.1 | c.1382T>C | p.Ile461Thr | missense_variant | 11/24 | ENSP00000518230 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461742Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727172
GnomAD4 genome Cov.: 33
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 | Jun 01, 2021 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DSP-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 461 of the DSP protein (p.Ile461Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. - |
Arrhythmogenic right ventricular dysplasia 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 20, 2019 | The DSP c.1382T>C (p.Ile461Thr) missense variant is located in the SH3 desmosome binding domain. A literature search was performed for the gene, cDNA, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database in a region of good sequencing coverage, so the variant is presumed to be rare. Based on the limited evidence, the p.Ile461Thr variant is classified as a variant of uncertain significance for arrhythmogenic right ventricular cardiomyopathy. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at