rs878854472
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000373960.4(DES):c.524G>A(p.Arg175His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,551,812 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 (★★). Synonymous variant affecting the same amino acid position (i.e. R175R) has been classified as Likely benign.
Frequency
Consequence
ENST00000373960.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DES | NM_001927.4 | c.524G>A | p.Arg175His | missense_variant | 1/9 | ENST00000373960.4 | NP_001918.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DES | ENST00000373960.4 | c.524G>A | p.Arg175His | missense_variant | 1/9 | 1 | NM_001927.4 | ENSP00000363071 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 33
GnomAD4 exome AF: 7.14e-7 AC: 1AN: 1399636Hom.: 0 Cov.: 92 AF XY: 0.00 AC XY: 0AN XY: 690666
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74332
ClinVar
Submissions by phenotype
Desmin-related myofibrillar myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 29, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DES protein function. ClinVar contains an entry for this variant (Variation ID: 239077). This variant has not been reported in the literature in individuals affected with DES-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 175 of the DES protein (p.Arg175His). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 17, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at