chrX-32644153-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4
The NM_004006.3(DMD):c.1310C>A(p.Ala437Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000183 in 1,094,967 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign 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. A437G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.1310C>A | p.Ala437Asp | missense_variant | 11/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.1310C>A | p.Ala437Asp | missense_variant | 11/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome AF: 0.00000183 AC: 2AN: 1094967Hom.: 0 Cov.: 29 AF XY: 0.00000277 AC XY: 1AN XY: 360583
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
Duchenne muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2021 | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 437 of the DMD protein (p.Ala437Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DMD-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | Nov 23, 2022 | The p.A437D variant (also known as c.1310C>A), located in coding exon 11 of the DMD gene, results from a C to A substitution at nucleotide position 1310. The alanine at codon 437 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is well 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 alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at