NM_004006.3:c.6438+44336C>A

Variant names:

• chrX-32172580-G-T
• rs1795588
• NM_004006.3:c.6438+44336C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004006.3(DMD):​c.6438+44336C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.72 (21216 hom., 22702 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 3 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMD	NM_004006.3	MANE Select	c.6438+44336C>A		intron	N/A	NP_003997.2
	DMD	NM_004009.3		c.6426+44336C>A		intron	N/A	NP_004000.1
	DMD	NM_000109.4		c.6414+44336C>A		intron	N/A	NP_000100.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMD	ENST00000357033.9	TSL:1 MANE Select	c.6438+44336C>A		intron	N/A	ENSP00000354923.3
	DMD	ENST00000378677.6	TSL:5	c.6426+44336C>A		intron	N/A	ENSP00000367948.2
	DMD	ENST00000619831.5	TSL:5	c.2406+44336C>A		intron	N/A	ENSP00000479270.2

Frequencies

GnomAD3 genomes AF: 0.716 AC: 78689 AN: 109836 Hom.: 21203 Cov.: 22

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.724

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.717 AC: 78757 AN: 109884 Hom.: 21216 Cov.: 22 AF XY: 0.706 AC XY: 22702 AN XY: 32156

African (AFR) AF: 0.942 AC: 28495 AN: 30265

American (AMR) AF: 0.781 AC: 7997 AN: 10242

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 1567 AN: 2625

East Asian (EAS) AF: 0.398 AC: 1367 AN: 3434

South Asian (SAS) AF: 0.558 AC: 1432 AN: 2567

European-Finnish (FIN) AF: 0.578 AC: 3313 AN: 5729

Middle Eastern (MID) AF: 0.651 AC: 138 AN: 212

European-Non Finnish (NFE) AF: 0.625 AC: 32893 AN: 52649

Other (OTH) AF: 0.729 AC: 1084 AN: 1486

Alfa AF: 0.658 Hom.: 62523

Bravo AF: 0.741

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.78
DANN	Benign	0.38
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1795588; hg19: chrX-32190697;