X-32172580-G-T

Position:

• chrX-32172580-G-T

Variant summary

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

The NM_004006.3(DMD):​c.6438+44336C>A 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 0.72 (21216 hom., 22702 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.6438+44336C>A		intron_variant		ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.6438+44336C>A		intron_variant		1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.716 AC: 78689 AN: 109836 Hom.: 21203 Cov.: 22 AF XY: 0.706 AC XY: 22649 AN XY: 32098

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.724

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: 0.717 AC: 78757 AN: 109884 Hom.: 21216 Cov.: 22 AF XY: 0.706 AC XY: 22702 AN XY: 32156

Gnomad4 AFR AF: 0.942

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.729

Alfa AF: 0.645 Hom.: 46076

Bravo AF: 0.741

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.78
DANN	Benign	0.38

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: rs1795588; hg19: chrX-32190697;