X-31120353-T-TCTTA

Position:

• chrX-31120353-T-TCTTA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004006.3(DMD):​c.*1565_*1566insTAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.087 (527 hom., 2375 hem., cov: 20)
  • Exomes 𝑓: 0.019 (0 hom. 1 hem.)
• Consequence: DMD NM_004006.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-31120353-T-TCTTA is Benign according to our data. Variant chrX-31120353-T-TCTTA is described in ClinVar as [Likely_benign]. Clinvar id is 368210.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.*1565_*1566insTAAG		3_prime_UTR_variant	79/79	ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.*1565_*1566insTAAG		3_prime_UTR_variant	79/79	1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 9573 AN: 110605 Hom.: 524 Cov.: 20 AF XY: 0.0716 AC XY: 2360 AN XY: 32959

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.00291

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00619

Gnomad FIN AF: 0.0268

Gnomad MID AF: 0.0551

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0683

GnomAD4 exome AF: 0.0195 AC: 5 AN: 257 Hom.: 0 Cov.: 0 AF XY: 0.0103 AC XY: 1 AN XY: 97

Gnomad4 FIN exome AF: 0.0198

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0867 AC: 9593 AN: 110654 Hom.: 527 Cov.: 20 AF XY: 0.0719 AC XY: 2375 AN XY: 33020

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00660

Gnomad4 FIN AF: 0.0268

Gnomad4 NFE AF: 0.0495

Gnomad4 OTH AF: 0.0675

Asia WGS AF: 0.0210 AC: 52 AN: 2522

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated cardiomyopathy 3B Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs758612124; hg19: chrX-31138470;