X-32389610-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004006.3(DMD):c.4409G>A(p.Arg1470His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,208,832 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. 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. R1470C) 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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.4409G>A | p.Arg1470His | missense_variant | Exon 32 of 79 | 1 | NM_004006.3 | ENSP00000354923.3 |
Frequencies
GnomAD3 genomes AF: 0.0000180 AC: 2AN: 111405Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33641
GnomAD3 exomes AF: 0.00000547 AC: 1AN: 182821Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67513
GnomAD4 exome AF: 0.0000155 AC: 17AN: 1097427Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 11AN XY: 362993
GnomAD4 genome AF: 0.0000180 AC: 2AN: 111405Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33641
ClinVar
Submissions by phenotype
not provided Uncertain:2
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Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Uncertain:1
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Cardiovascular phenotype Uncertain:1
The p.R1470H variant (also known as c.4409G>A), located in coding exon 32 of the DMD gene, results from a G to A substitution at nucleotide position 4409. The arginine at codon 1470 is replaced by histidine, an amino acid with highly similar properties. Based on data from gnomAD, the A allele has an overall frequency of <0.01% (1/182821) total alleles studied, with 1 hemizygote(s) observed. The highest observed frequency was <0.01% (1/81465) of European (non-Finnish) alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. -
Duchenne muscular dystrophy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at