chrX-32342158-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004006.3(DMD):c.5864G>A(p.Arg1955His) variant causes a missense change. The variant allele was found at a frequency of 0.0000182 in 1,208,327 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. 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. R1955C) has been classified as Uncertain significance.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.5864G>A | p.Arg1955His | missense_variant | 41/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.5864G>A | p.Arg1955His | missense_variant | 41/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000895 AC: 1AN: 111764Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33966
GnomAD3 exomes AF: 0.0000220 AC: 4AN: 181902Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 66650
GnomAD4 exome AF: 0.0000192 AC: 21AN: 1096511Hom.: 0 Cov.: 31 AF XY: 0.0000166 AC XY: 6AN XY: 362067
GnomAD4 genome AF: 0.00000894 AC: 1AN: 111816Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34030
ClinVar
Submissions by phenotype
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 06, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 07, 2017 | - - |
Duchenne muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1955 of the DMD protein (p.Arg1955His). This variant is present in population databases (rs200455300, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 518775). 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 not expected to disrupt DMD protein function with a negative predictive value of 95%. 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 | Jan 14, 2016 | The p.R1955H variant (also known as c.5864G>A), located in coding exon 41 of the DMD gene, results from a G to A substitution at nucleotide position 5864. The arginine at codon 1955 is replaced by histidine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs200455300. Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0% (0/503) total male alleles studied. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at