rs1060502624
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_004006.3(DMD):c.9238_9241del(p.Thr3080LeufsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Consequence
DMD
NM_004006.3 frameshift
NM_004006.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.06
Genes affected
DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant X-31260999-GTTGT-G is Pathogenic according to our data. Variant chrX-31260999-GTTGT-G is described in ClinVar as [Pathogenic]. Clinvar id is 409893.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-31260999-GTTGT-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.9238_9241del | p.Thr3080LeufsTer8 | frameshift_variant | 63/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.9238_9241del | p.Thr3080LeufsTer8 | frameshift_variant | 63/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Duchenne muscular dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 23, 2016 | While this particular variant has not been reported in the literature, truncating variants in DMD are known to be pathogenic (PMID: 25007885). This variant has been reported in the DMD Leiden Open-source Variation Database (PMID: 21520333). For these reasons, this variant has been classified as Pathogenic. This sequence change deletes 4 nucleotides from exon 63 of the DMD mRNA (c.9238_9241delACAA), causing a frameshift at codon 3080. This creates a premature translational stop signal (p.Thr3080Leufs*8) and is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at