rs748742357
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_001927.4(DES):c.943C>T(p.Arg315Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,704 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R315H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001927.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DES | NM_001927.4 | c.943C>T | p.Arg315Cys | missense_variant | 5/9 | ENST00000373960.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DES | ENST00000373960.4 | c.943C>T | p.Arg315Cys | missense_variant | 5/9 | 1 | NM_001927.4 | P1 | |
DES | ENST00000477226.6 | n.417C>T | non_coding_transcript_exon_variant | 4/8 | 4 | ||||
DES | ENST00000492726.1 | n.338C>T | non_coding_transcript_exon_variant | 4/6 | 4 | ||||
DES | ENST00000683013.1 | n.331C>T | non_coding_transcript_exon_variant | 3/7 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251060Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135728
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461646Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1AN XY: 727152
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74262
ClinVar
Submissions by phenotype
Desmin-related myofibrillar myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 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. 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) performed at Invitae indicates that this missense variant is expected to disrupt DES protein function. ClinVar contains an entry for this variant (Variation ID: 541302). This variant has not been reported in the literature in individuals affected with DES-related conditions. This variant is present in population databases (rs748742357, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 315 of the DES protein (p.Arg315Cys). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 10, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at