rs377152944

chrX-31266835-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The ENST00000378723.7(DMD):c.-6G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000541 in 1,204,289 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 202 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., 11 hem., cov: 22)
  • Exomes 𝑓: 0.00056 (0 hom. 191 hem.)
• Consequence: DMD ENST00000378723.7 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.744

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BS2: High Hemizygotes in GnomAd at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.9225-5819G>T		intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.9225-5819G>T		intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.000305 AC: 34 AN: 111311 Hom.: 0 Cov.: 22 AF XY: 0.000327 AC XY: 11 AN XY: 33653

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000936

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000624

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000340 AC: 57 AN: 167649 Hom.: 0 AF XY: 0.000354 AC XY: 20 AN XY: 56455

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000702

Gnomad NFE exome AF: 0.000766

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000565 AC: 617 AN: 1092934 Hom.: 0 Cov.: 30 AF XY: 0.000532 AC XY: 191 AN XY: 359350

Gnomad4 AFR exome AF: 0.0000761

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000175

Gnomad4 NFE exome AF: 0.000675

Gnomad4 OTH exome AF: 0.000895

GnomAD4 genome AF: 0.000305 AC: 34 AN: 111355 Hom.: 0 Cov.: 22 AF XY: 0.000326 AC XY: 11 AN XY: 33707

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000935

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000624

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000564 Hom.: 3

Bravo AF: 0.000276

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 23, 2015

Variant classified as Uncertain Significance - Favor Benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	18
Dann	Benign	0.94

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: rs377152944; hg19: chrX-31284952;