rs749155619
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_004415.4(DSP):c.386G>A(p.Arg129Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129W) has been classified 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.386G>A | p.Arg129Gln | missense_variant | 3/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.386G>A | p.Arg129Gln | missense_variant | 3/24 | ||
DSP | NM_001008844.3 | c.386G>A | p.Arg129Gln | missense_variant | 3/24 | ||
DSP | NM_001406591.1 | c.386G>A | p.Arg129Gln | missense_variant | 3/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.386G>A | p.Arg129Gln | missense_variant | 3/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.386G>A | p.Arg129Gln | missense_variant | 3/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.386G>A | p.Arg129Gln | missense_variant | 3/24 | A2 | |||
DSP | ENST00000683563.1 | n.278G>A | non_coding_transcript_exon_variant | 3/4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251396Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135882
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.0000234 AC XY: 17AN XY: 727238
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 24, 2023 | This missense variant replaces arginine with glutamine at codon 129 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with DSP-related disorders in the literature. This variant has been identified in 3/251396 chromosomes 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. - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Nov 17, 2017 | - - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 19, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at