rs722576

Variant names:

• chrX-32317045-T-A
• rs722576
• NM_004006.3:c.5923-6769A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-32317045-T-A
• chrX-32317045-T-C
• chrX-32317045-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004006.3(DMD):​c.5923-6769A>T 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 0.74 (21349 hom., 23437 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 0 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3	c.5923-6769A>T		intron_variant	Intron 41 of 78	ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.5923-6769A>T		intron_variant	Intron 41 of 78	1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.737 AC: 80700 AN: 109520 Hom.: 21360 Cov.: 22

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.773

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: 0.737 AC: 80713 AN: 109575 Hom.: 21349 Cov.: 22 AF XY: 0.732 AC XY: 23437 AN XY: 32033

African (AFR) AF: 0.659 AC: 19923 AN: 30255

American (AMR) AF: 0.807 AC: 8221 AN: 10184

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2158 AN: 2626

East Asian (EAS) AF: 0.719 AC: 2470 AN: 3437

South Asian (SAS) AF: 0.820 AC: 2121 AN: 2587

European-Finnish (FIN) AF: 0.686 AC: 3926 AN: 5726

Middle Eastern (MID) AF: 0.744 AC: 151 AN: 203

European-Non Finnish (NFE) AF: 0.767 AC: 40171 AN: 52380

Other (OTH) AF: 0.765 AC: 1147 AN: 1500

Alfa AF: 0.759 Hom.: 6250

Bravo AF: 0.737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.70
PhyloP100		2.0
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: rs722576; hg19: chrX-32335162;