chrX-32411903-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004006.3(DMD):āc.4082G>Cā(p.Arg1361Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000331 in 1,208,609 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1361K) 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.4082G>C | p.Arg1361Thr | missense_variant | 30/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.4082G>C | p.Arg1361Thr | missense_variant | 30/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000899 AC: 1AN: 111182Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1AN XY: 33410
GnomAD4 exome AF: 0.00000273 AC: 3AN: 1097427Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 362939
GnomAD4 genome AF: 0.00000899 AC: 1AN: 111182Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1AN XY: 33410
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 28, 2015 | The p.Arg1361Thr variant in DMD has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction too ls and conservation analysis do not provide strong support for or against an imp act to the protein. In summary, the clinical significance of the p.Arg1361Thr va riant is uncertain. - |
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 31, 2019 | - - |
Duchenne muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This variant has not been reported in the literature in individuals affected with DMD-related conditions. 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 not expected to disrupt DMD protein function. ClinVar contains an entry for this variant (Variation ID: 228587). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 1361 of the DMD protein (p.Arg1361Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at