rs41303181

Variant names:

• chrX-32390194-T-C
• rs41303181
• NM_004006.3:c.4234-13A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004006.3(DMD):​c.4234-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,117,038 control chromosomes in the GnomAD database, including 2,092 homozygotes. There are 24,362 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (183 hom., 1735 hem., cov: 23)
  • Exomes 𝑓: 0.072 (1909 hom. 22627 hem.)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -3.88
• Publications: 5 publications found

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]

DMD Gene-Disease associations (from GenCC):

• Becker muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• dilated cardiomyopathy 3B

  Inheritance: XL Classification: DEFINITIVE Submitted by: Ambry Genetics
• Duchenne and Becker muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• Duchenne muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• progressive muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-32390194-T-C is Benign according to our data. Variant chrX-32390194-T-C is described in ClinVar as Benign. ClinVar VariationId is 94617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004006.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMD	NM_004006.3	MANE Select	c.4234-13A>G		intron	N/A	NP_003997.2	P11532-1
	DMD	NM_004009.3		c.4222-13A>G		intron	N/A	NP_004000.1	P11532
	DMD	NM_000109.4		c.4210-13A>G		intron	N/A	NP_000100.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMD	ENST00000357033.9	TSL:1 MANE Select	c.4234-13A>G		intron	N/A	ENSP00000354923.3	P11532-1
	DMD	ENST00000378677.6	TSL:5	c.4222-13A>G		intron	N/A	ENSP00000367948.2	P11532-11
	DMD	ENST00000619831.5	TSL:5	c.202-13A>G		intron	N/A	ENSP00000479270.2	A0A087WV90

Frequencies

GnomAD3 genomes AF: 0.0529 AC: 5884 AN: 111143 Hom.: 184 Cov.: 23

Gnomad AFR AF: 0.00986

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.000846

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0795

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.0641

GnomAD2 exomes AF: 0.0607 AC: 10958 AN: 180502 AF XY: 0.0622

Gnomad AFR exome AF: 0.00848

Gnomad AMR exome AF: 0.0499

Gnomad ASJ exome AF: 0.0837

Gnomad EAS exome AF: 0.000146

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.0743

Gnomad OTH exome AF: 0.0679

GnomAD4 exome AF: 0.0723 AC: 72692 AN: 1005841 Hom.: 1909 Cov.: 22 AF XY: 0.0778 AC XY: 22627 AN XY: 290821

African (AFR) AF: 0.00944 AC: 233 AN: 24688

American (AMR) AF: 0.0487 AC: 1708 AN: 35048

Ashkenazi Jewish (ASJ) AF: 0.0872 AC: 1640 AN: 18805

East Asian (EAS) AF: 0.000505 AC: 15 AN: 29703

South Asian (SAS) AF: 0.0429 AC: 2226 AN: 51919

European-Finnish (FIN) AF: 0.118 AC: 4768 AN: 40252

Middle Eastern (MID) AF: 0.0579 AC: 226 AN: 3903

European-Non Finnish (NFE) AF: 0.0779 AC: 59072 AN: 758551

Other (OTH) AF: 0.0653 AC: 2804 AN: 42972

GnomAD4 genome AF: 0.0529 AC: 5881 AN: 111197 Hom.: 183 Cov.: 23 AF XY: 0.0519 AC XY: 1735 AN XY: 33405

African (AFR) AF: 0.00984 AC: 302 AN: 30688

American (AMR) AF: 0.0503 AC: 523 AN: 10403

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 241 AN: 2637

East Asian (EAS) AF: 0.000848 AC: 3 AN: 3536

South Asian (SAS) AF: 0.0312 AC: 82 AN: 2630

European-Finnish (FIN) AF: 0.107 AC: 636 AN: 5936

Middle Eastern (MID) AF: 0.0826 AC: 18 AN: 218

European-Non Finnish (NFE) AF: 0.0745 AC: 3944 AN: 52963

Other (OTH) AF: 0.0639 AC: 96 AN: 1503

Alfa AF: 0.0561 Hom.: 806

Bravo AF: 0.0484

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Dilated cardiomyopathy 3B (2)
-	-	2	Duchenne muscular dystrophy (2)
-	-	2	not provided (2)
-	-	1	Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0050
DANN	Benign	0.32
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41303181; hg19: chrX-32408311;