rs10521966

chrX-31298518-T-G

Variant summary

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

The NM_004006.3(DMD):c.9224+25080A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 110,376 control chromosomes in the GnomAD database, including 5,826 homozygotes. There are 10,246 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 0.34 (5826 hom., 10246 hem., cov: 22)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

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=-0.86).
• BP6: Variant X-31298518-T-G is Benign according to our data. Variant chrX-31298518-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.9224+25080A>C		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.9224+25080A>C		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 37129 AN: 110325 Hom.: 5824 Cov.: 22 AF XY: 0.313 AC XY: 10214 AN XY: 32581

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.00532

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.337 AC: 37163 AN: 110376 Hom.: 5826 Cov.: 22 AF XY: 0.314 AC XY: 10246 AN XY: 32642

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.00533

Gnomad4 SAS AF: 0.0992

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.286

Alfa AF: 0.280 Hom.: 5802

Bravo AF: 0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.6
Dann	Benign	0.62

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: rs10521966; hg19: chrX-31316635;