rs10521969

chrX-31437239-C-AchrX-31437239-C-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.9084+7242G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0576 in 111,867 control chromosomes in the GnomAD database, including 271 homozygotes. There are 1,822 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 0.058 (271 hom., 1822 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.9).
• BP6: Variant X-31437239-C-A is Benign according to our data. Variant chrX-31437239-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.9084+7242G>T		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.9084+7242G>T		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 6433 AN: 111816 Hom.: 271 Cov.: 23 AF XY: 0.0534 AC XY: 1817 AN XY: 34036

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.0491

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.0708

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0576 AC: 6442 AN: 111867 Hom.: 271 Cov.: 23 AF XY: 0.0534 AC XY: 1822 AN XY: 34097

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0451

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.0490

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.0213

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0708

Alfa AF: 0.0136 Hom.: 71

Bravo AF: 0.0643

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.041
Dann	Benign	0.52

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: rs10521969; hg19: chrX-31455356;