X-32385620-T-TAATTTTACACCATCAAAGCTCTA

Variant names:

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

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+690insTAGAGCTTTGATGGTGTAAAATT 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 0.000028 (0 hom., 0 hem., cov: 0)
• 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
• 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMD	NM_004006.3	MANE Select	c.4674+689_4674+690insTAGAGCTTTGATGGTGTAAAATT		intron	N/A	NP_003997.2
	DMD	NM_004009.3		c.4662+689_4662+690insTAGAGCTTTGATGGTGTAAAATT		intron	N/A	NP_004000.1
	DMD	NM_000109.4		c.4650+689_4650+690insTAGAGCTTTGATGGTGTAAAATT		intron	N/A	NP_000100.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMD	ENST00000357033.9	TSL:1 MANE Select	c.4674+689_4674+690insTAGAGCTTTGATGGTGTAAAATT		intron	N/A	ENSP00000354923.3
	DMD	ENST00000378677.6	TSL:5	c.4662+689_4662+690insTAGAGCTTTGATGGTGTAAAATT		intron	N/A	ENSP00000367948.2
	DMD	ENST00000619831.5	TSL:5	c.642+689_642+690insTAGAGCTTTGATGGTGTAAAATT		intron	N/A	ENSP00000479270.2

Frequencies

GnomAD3 genomes AF: 0.0000277 AC: 3 AN: 108342 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00119

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000277 AC: 3 AN: 108390 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 31214

African (AFR) AF: 0.00 AC: 0 AN: 29823

American (AMR) AF: 0.00 AC: 0 AN: 10045

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2594

East Asian (EAS) AF: 0.00 AC: 0 AN: 3431

South Asian (SAS) AF: 0.00119 AC: 3 AN: 2520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 211

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51962

Other (OTH) AF: 0.00 AC: 0 AN: 1463

Alfa AF: 0.00 Hom.: 1292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.083

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;