rs753460206
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_004006.3(DMD):c.10593C>T(p.His3531His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,092,909 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.000019 ( 0 hom., 2 hem., cov: 21)
Exomes 𝑓: 0.000013 ( 0 hom. 6 hem. )
Failed GnomAD Quality Control
Consequence
DMD
NM_004006.3 synonymous
NM_004006.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.25
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant X-31147479-G-A is Benign according to our data. Variant chrX-31147479-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 415853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.25 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 6 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.10593C>T | p.His3531His | synonymous_variant | 75/79 | ENST00000357033.9 | NP_003997.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.10593C>T | p.His3531His | synonymous_variant | 75/79 | 1 | NM_004006.3 | ENSP00000354923.3 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 2AN: 107954Hom.: 0 Cov.: 21 AF XY: 0.0000655 AC XY: 2AN XY: 30534 FAILED QC
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GnomAD3 exomes AF: 0.0000562 AC: 10AN: 177962Hom.: 0 AF XY: 0.0000634 AC XY: 4AN XY: 63050
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GnomAD4 exome AF: 0.0000128 AC: 14AN: 1092909Hom.: 0 Cov.: 29 AF XY: 0.0000167 AC XY: 6AN XY: 358551
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000185 AC: 2AN: 108004Hom.: 0 Cov.: 21 AF XY: 0.0000654 AC XY: 2AN XY: 30594
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 15, 2017 | - - |
Duchenne muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 08, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 12, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at