X-31204460-T-C

Position:

• chrX-31204460-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The ENST00000357033.9(DMD):​c.9650-342A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.59 (13992 hom., 19706 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: DMD ENST00000357033.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-31204460-T-C is Benign according to our data. Variant chrX-31204460-T-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.9650-342A>G		intron_variant		ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.9650-342A>G		intron_variant		1	NM_004006.3	ENSP00000354923	P4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 65672 AN: 110677 Hom.: 13996 Cov.: 23 AF XY: 0.598 AC XY: 19673 AN XY: 32919

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.609

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.592

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.593 AC: 65696 AN: 110735 Hom.: 13992 Cov.: 23 AF XY: 0.597 AC XY: 19706 AN XY: 32987

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.592

Alfa AF: 0.605 Hom.: 7604

Bravo AF: 0.585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs5927701; hg19: chrX-31222577;