rs368326458
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004006.3(DMD):c.1537A>G(p.Met513Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,088,332 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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. M513I) has been classified as Uncertain significance.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.1537A>G | p.Met513Val | missense_variant | 13/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.1537A>G | p.Met513Val | missense_variant | 13/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 112058Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34224 FAILED QC
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183249Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67721
GnomAD4 exome AF: 0.00000276 AC: 3AN: 1088332Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 354098
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 112058Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34224
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. | Sep 29, 2018 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 07, 2021 | The p.M513V variant (also known as c.1537A>G), located in coding exon 13 of the DMD gene, results from an A to G substitution at nucleotide position 1537. The methionine at codon 513 is replaced by valine, an amino acid with highly similar properties. Based on data from gnomAD, the G allele has an overall frequency of 0.0005% (1/183249) total alleles studied, with no hemizygotes observed. The highest observed frequency was 0.007% (1/13153) of African/African-American alleles. This amino acid position is highly conserved in available vertebrate species. 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. - |
Duchenne muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 16, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 513 of the DMD protein (p.Met513Val). This variant is present in population databases (rs368326458, 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: 455864). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at