rs5972556

Variant names:

• chrX-32394097-G-A
• rs5972556
• NM_004006.3:c.4234-3916C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-32394097-G-A
• chrX-32394097-G-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.4234-3916C>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 0.56 (12289 hom., 18501 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 1 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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3	c.4234-3916C>T		intron_variant	Intron 30 of 78	ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.4234-3916C>T		intron_variant	Intron 30 of 78	1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.561 AC: 61924 AN: 110409 Hom.: 12293 Cov.: 23

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.573

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: 0.561 AC: 61944 AN: 110459 Hom.: 12289 Cov.: 23 AF XY: 0.565 AC XY: 18501 AN XY: 32765

African (AFR) AF: 0.558 AC: 16953 AN: 30400

American (AMR) AF: 0.686 AC: 7151 AN: 10419

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 1538 AN: 2636

East Asian (EAS) AF: 0.781 AC: 2729 AN: 3493

South Asian (SAS) AF: 0.632 AC: 1670 AN: 2642

European-Finnish (FIN) AF: 0.589 AC: 3366 AN: 5717

Middle Eastern (MID) AF: 0.453 AC: 96 AN: 212

European-Non Finnish (NFE) AF: 0.518 AC: 27328 AN: 52769

Other (OTH) AF: 0.569 AC: 852 AN: 1498

Alfa AF: 0.534 Hom.: 70320

Bravo AF: 0.573

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.19
PhyloP100		0.24
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: rs5972556; hg19: chrX-32412214;