NM_004006.3:c.4071+2012T>C

Variant names:

• chrX-32436229-A-G
• rs2405829
• NM_004006.3:c.4071+2012T>C

Variant summary

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

The NM_004006.3(DMD):​c.4071+2012T>C 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 0.49 (9662 hom., 15854 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 4 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=-1.0).

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.4071+2012T>C		intron	N/A	NP_003997.2
	DMD	NM_004009.3		c.4059+2012T>C		intron	N/A	NP_004000.1
	DMD	NM_000109.4		c.4047+2012T>C		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.4071+2012T>C		intron	N/A	ENSP00000354923.3
	DMD	ENST00000378677.6	TSL:5	c.4059+2012T>C		intron	N/A	ENSP00000367948.2
	DMD	ENST00000420596.5	TSL:5	c.94-71030T>C		intron	N/A	ENSP00000399897.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 54200 AN: 110148 Hom.: 9670 Cov.: 22

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.482

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: 0.492 AC: 54222 AN: 110200 Hom.: 9662 Cov.: 22 AF XY: 0.488 AC XY: 15854 AN XY: 32486

African (AFR) AF: 0.537 AC: 16276 AN: 30288

American (AMR) AF: 0.462 AC: 4779 AN: 10347

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1046 AN: 2627

East Asian (EAS) AF: 0.755 AC: 2597 AN: 3438

South Asian (SAS) AF: 0.502 AC: 1284 AN: 2556

European-Finnish (FIN) AF: 0.560 AC: 3242 AN: 5785

Middle Eastern (MID) AF: 0.425 AC: 91 AN: 214

European-Non Finnish (NFE) AF: 0.456 AC: 24084 AN: 52767

Other (OTH) AF: 0.477 AC: 719 AN: 1506

Alfa AF: 0.460 Hom.: 41284

Bravo AF: 0.497

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.66
PhyloP100		-0.086
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: rs2405829; hg19: chrX-32454346;