rs10522006

Positions:

• chrX-32569413-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004006.3(DMD):​c.1813-3532C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 110,740 control chromosomes in the GnomAD database, including 8,449 homozygotes. There are 13,610 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.42 (8449 hom., 13610 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-32569413-G-T is Benign according to our data. Variant chrX-32569413-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.1813-3532C>A		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.1813-3532C>A		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.421 AC: 46628 AN: 110685 Hom.: 8454 Cov.: 23 AF XY: 0.413 AC XY: 13584 AN XY: 32907

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.421 AC: 46643 AN: 110740 Hom.: 8449 Cov.: 23 AF XY: 0.413 AC XY: 13610 AN XY: 32972

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.430

Alfa AF: 0.537 Hom.: 45429

Bravo AF: 0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.27
DANN	Benign	0.45

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: rs10522006; hg19: chrX-32587530;