NM_004006.3:c.3432+1266T>C

Variant names:

• chrX-32462173-A-G
• rs5972577
• NM_004006.3:c.3432+1266T>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.3432+1266T>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 0.68 (18258 hom., 21897 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• 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=-1.06).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3	c.3432+1266T>C		intron_variant	Intron 25 of 78	ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.3432+1266T>C		intron_variant	Intron 25 of 78	1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.683 AC: 74776 AN: 109466 Hom.: 18263 Cov.: 22

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.629

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.686

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: 0.683 AC: 74803 AN: 109517 Hom.: 18258 Cov.: 22 AF XY: 0.688 AC XY: 21897 AN XY: 31845

African (AFR) AF: 0.668 AC: 20148 AN: 30159

American (AMR) AF: 0.782 AC: 7984 AN: 10206

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1508 AN: 2621

East Asian (EAS) AF: 0.868 AC: 2984 AN: 3439

South Asian (SAS) AF: 0.752 AC: 1914 AN: 2545

European-Finnish (FIN) AF: 0.813 AC: 4629 AN: 5697

Middle Eastern (MID) AF: 0.620 AC: 134 AN: 216

European-Non Finnish (NFE) AF: 0.652 AC: 34250 AN: 52493

Other (OTH) AF: 0.679 AC: 1001 AN: 1475

Alfa AF: 0.659 Hom.: 58685

Bravo AF: 0.688

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.34
DANN	Benign	0.36
PhyloP100		-1.7
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: rs5972577; hg19: chrX-32480290;