rs5972577

chrX-32462173-A-GchrX-32462173-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004006.3(DMD):c.3432+1266T>C 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 0.68 (18258 hom., 21897 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BS2: High Homozygotes in GnomAd at 18263 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.3432+1266T>C		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.3432+1266T>C		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.683 AC: 74776 AN: 109466 Hom.: 18263 Cov.: 22 AF XY: 0.688 AC XY: 21856 AN XY: 31784

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.629

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.686

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: 0.683 AC: 74803 AN: 109517 Hom.: 18258 Cov.: 22 AF XY: 0.688 AC XY: 21897 AN XY: 31845

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.679

Alfa AF: 0.657 Hom.: 43431

Bravo AF: 0.688

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.34
Dann	Benign	0.36

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: rs5972577; hg19: chrX-32480290;