rs879254348
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The ENST00000379802.8(DSP):āc.5697C>Gā(p.Ile1899Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. I1899I) has been classified as Likely benign.
Frequency
Consequence
ENST00000379802.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.5697C>G | p.Ile1899Met | missense_variant | 24/24 | ENST00000379802.8 | NP_004406.2 | |
DSP | NM_001319034.2 | c.4368C>G | p.Ile1456Met | missense_variant | 24/24 | NP_001305963.1 | ||
DSP | NM_001008844.3 | c.3900C>G | p.Ile1300Met | missense_variant | 24/24 | NP_001008844.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.5697C>G | p.Ile1899Met | missense_variant | 24/24 | 1 | NM_004415.4 | ENSP00000369129 | P2 | |
DSP | ENST00000418664.2 | c.3900C>G | p.Ile1300Met | missense_variant | 24/24 | 1 | ENSP00000396591 | A2 | ||
DSP | ENST00000710359.1 | c.4368C>G | p.Ile1456Met | missense_variant | 24/24 | ENSP00000518230 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251130Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135764
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461854Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727234
GnomAD4 genome Cov.: 32
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 | Sep 05, 2021 | This sequence change replaces isoleucine with methionine at codon 1899 of the DSP protein (p.Ile1899Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with DSP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 01, 2023 | The p.I1899M variant (also known as c.5697C>G), located in coding exon 24 of the DSP gene, results from a C to G substitution at nucleotide position 5697. The isoleucine at codon 1899 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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