rs398123937
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_004006.3(DMD):c.3432+1G>A variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_004006.3 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.3432+1G>A | splice_donor_variant, intron_variant | Intron 25 of 78 | 1 | NM_004006.3 | ENSP00000354923.3 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD4 exome Cov.: 28
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
not provided Pathogenic:2
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Duchenne muscular dystrophy Pathogenic:2
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This sequence change affects a donor splice site in intron 25 of the DMD gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Becker muscular dystrophy (PMID: 16834926, 19001018, 19783145). This variant is also known as IVS25+1G>A. ClinVar contains an entry for this variant (Variation ID: 94589). Studies have shown that disruption of this splice site results in skipping of exon 25, but is expected to preserve the integrity of the reading-frame (PMID: 19001018, 19783145). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at