rs3764764
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004006.3(DMD):c.94-9T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,093,641 control chromosomes in the GnomAD database, including 2 homozygotes. There are 92 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., 8 hem., cov: 20)
Exomes 𝑓: 0.00023 ( 2 hom. 84 hem. )
Consequence
DMD
NM_004006.3 splice_polypyrimidine_tract, intron
NM_004006.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.01118
2
Clinical Significance
Conservation
PhyloP100: 0.00
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant X-32849829-A-T is Benign according to our data. Variant chrX-32849829-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 377773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-32849829-A-T is described in Lovd as [Benign]. Variant chrX-32849829-A-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00035 (33/94316) while in subpopulation EAS AF= 0.00249 (7/2811). AF 95% confidence interval is 0.00117. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 8 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.94-9T>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.94-9T>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000361 AC: 34AN: 94260Hom.: 0 Cov.: 20 AF XY: 0.000263 AC XY: 8AN XY: 30420
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GnomAD3 exomes AF: 0.000733 AC: 112AN: 152880Hom.: 0 AF XY: 0.000688 AC XY: 40AN XY: 58112
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GnomAD4 exome AF: 0.000231 AC: 231AN: 999325Hom.: 2 Cov.: 23 AF XY: 0.000291 AC XY: 84AN XY: 288329
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GnomAD4 genome ? AF: 0.000350 AC: 33AN: 94316Hom.: 0 Cov.: 20 AF XY: 0.000263 AC XY: 8AN XY: 30476
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 01, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 12, 2024 | - - |
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 19, 2019 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 27, 2019 | - - |
Duchenne muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at