X-32387899-T-C

Position:

• chrX-32387899-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004006.3(DMD):​c.4519-1434A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (23397 hom., 24784 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.4519-1434A>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.4519-1434A>G		intron_variant		1	NM_004006.3	ENSP00000354923	P4

Frequencies

GnomAD3 genomes AF: 0.773 AC: 84802 AN: 109746 Hom.: 23402 Cov.: 22 AF XY: 0.770 AC XY: 24739 AN XY: 32140

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.766

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: 0.773 AC: 84833 AN: 109802 Hom.: 23397 Cov.: 22 AF XY: 0.770 AC XY: 24784 AN XY: 32206

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.758

Alfa AF: 0.739 Hom.: 19994

Bravo AF: 0.783

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.77

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: rs1555256; hg19: chrX-32406016;