chrX-32464159-A-G

Position:

• chrX-32464159-A-G

Variant summary

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

The NM_004006.3(DMD):​c.3276+427T>C 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 0.74 (21291 hom., 24368 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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]

DMD (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant X-32464159-A-G is Benign according to our data. Variant chrX-32464159-A-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.3276+427T>C		intron_variant		ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.3276+427T>C		intron_variant		1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.739 AC: 81649 AN: 110555 Hom.: 21295 Cov.: 23 AF XY: 0.742 AC XY: 24328 AN XY: 32791

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.689

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.743

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: 0.738 AC: 81676 AN: 110604 Hom.: 21291 Cov.: 23 AF XY: 0.742 AC XY: 24368 AN XY: 32850

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.804

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.735

Alfa AF: 0.665 Hom.: 5433

Bravo AF: 0.742

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.59
DANN	Benign	0.82

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: rs228388; hg19: chrX-32482276;