rs730880074

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000357033.9(DMD):​c.6118-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 9.5e-7 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

DMD
ENST00000357033.9 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0006940
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.26
Variant links:
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DMDNM_004006.3 linkuse as main transcriptc.6118-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000357033.9 NP_003997.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DMDENST00000357033.9 linkuse as main transcriptc.6118-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_004006.3 ENSP00000354923 P4

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
9.55e-7
AC:
1
AN:
1047442
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
325258
show subpopulations
Gnomad4 AFR exome
AF:
0.0000407
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
11
DANN
Benign
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00069
dbscSNV1_RF
Benign
0.034
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs730880074; hg19: chrX-32305821; API