X-32385620-T-TAATTTTAAACCATCAAAGCTCTA

Variant names:

• chrX-32385620-T-TAATTTTAAACCATCAAAGCTCTA
• rs6151281
• NM_004006.3:c.4674+689_4674+690insTAGAGCTTTGATGGTTTAAAATT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004006.3(DMD):​c.4674+689_4674+690insTAGAGCTTTGATGGTTTAAAATT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (19289 hom., 20976 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3	c.4674+689_4674+690insTAGAGCTTTGATGGTTTAAAATT		intron_variant	Intron 33 of 78	ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.4674+689_4674+690insTAGAGCTTTGATGGTTTAAAATT		intron_variant	Intron 33 of 78	1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes AF: 0.694 AC: 74855 AN: 107789 Hom.: 19288 Cov.: 0

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.550

Gnomad NFE AF: 0.608

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: 0.694 AC: 74885 AN: 107837 Hom.: 19289 Cov.: 0 AF XY: 0.683 AC XY: 20976 AN XY: 30715

African (AFR) AF: 0.835 AC: 24802 AN: 29702

American (AMR) AF: 0.748 AC: 7481 AN: 10007

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1385 AN: 2580

East Asian (EAS) AF: 0.774 AC: 2618 AN: 3384

South Asian (SAS) AF: 0.709 AC: 1782 AN: 2513

European-Finnish (FIN) AF: 0.711 AC: 3982 AN: 5597

Middle Eastern (MID) AF: 0.550 AC: 115 AN: 209

European-Non Finnish (NFE) AF: 0.608 AC: 31449 AN: 51728

Other (OTH) AF: 0.679 AC: 988 AN: 1455

Alfa AF: 0.429 Hom.: 1292

Asia WGS AF: 0.707 AC: 1779 AN: 2518

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.083
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6151281; hg19: chrX-32403737;