rs886043324
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_004006.3(DMD):āc.10592A>Gā(p.His3531Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000258 in 1,201,560 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H3531D) has been classified as Likely benign.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.10592A>G | p.His3531Arg | missense_variant | 75/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.10592A>G | p.His3531Arg | missense_variant | 75/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000369 AC: 4AN: 108351Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 30787
GnomAD3 exomes AF: 0.0000169 AC: 3AN: 177679Hom.: 0 AF XY: 0.0000319 AC XY: 2AN XY: 62765
GnomAD4 exome AF: 0.0000247 AC: 27AN: 1093209Hom.: 0 Cov.: 29 AF XY: 0.0000446 AC XY: 16AN XY: 358827
GnomAD4 genome ? AF: 0.0000369 AC: 4AN: 108351Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 30787
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 23, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 14, 2017 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 24, 2023 | The p.H3531R variant (also known as c.10592A>G), located in coding exon 75 of the DMD gene, results from an A to G substitution at nucleotide position 10592. The histidine at codon 3531 is replaced by arginine, an amino acid with highly similar properties. Based on data from gnomAD, the G allele has an overall frequency of 0.003% (5/198759) total alleles studied, with 2 hemizygote(s) observed. The highest observed frequency was 0.006% (5/89009) of European (non-Finnish) alleles. 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 alteration remains unclear. - |
Duchenne muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at