X-31330690-G-T

Position:

• chrX-31330690-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004006.3(DMD):​c.9164-7032C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 110,920 control chromosomes in the GnomAD database, including 1,481 homozygotes. There are 6,060 hemizygotes in GnomAD. 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 0.19 (1481 hom., 6060 hem., cov: 23)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.9164-7032C>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.9164-7032C>A		intron_variant		1	NM_004006.3	ENSP00000354923	P4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 20713 AN: 110870 Hom.: 1483 Cov.: 23 AF XY: 0.183 AC XY: 6057 AN XY: 33158

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.187 AC: 20706 AN: 110920 Hom.: 1481 Cov.: 23 AF XY: 0.182 AC XY: 6060 AN XY: 33218

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.193

Alfa AF: 0.117 Hom.: 1258

Bravo AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.044
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: rs12557137; hg19: chrX-31348807;