rs3764764

chrX-32849829-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004006.3(DMD):c.94-9T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,093,641 control chromosomes in the GnomAD database, including 2 homozygotes. There are 92 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., 8 hem., cov: 20)
  • Exomes 𝑓: 0.00023 (2 hom. 84 hem.)
• Consequence: DMD NM_004006.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.01118
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-32849829-A-T is Benign according to our data. Variant chrX-32849829-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 377773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-32849829-A-T is described in Lovd as [Benign]. Variant chrX-32849829-A-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00035 (33/94316) while in subpopulation EAS AF= 0.00249 (7/2811). AF 95% confidence interval is 0.00117. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.94-9T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.94-9T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 34 AN: 94260 Hom.: 0 Cov.: 20 AF XY: 0.000263 AC XY: 8 AN XY: 30420

Gnomad AFR AF: 0.000214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000993

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00283

Gnomad SAS AF: 0.000412

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000209

Gnomad OTH AF: 0.000815

GnomAD3 exomes AF: 0.000733 AC: 112 AN: 152880 Hom.: 0 AF XY: 0.000688 AC XY: 40 AN XY: 58112

Gnomad AFR exome AF: 0.000417

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00547

Gnomad SAS exome AF: 0.000610

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000135

Gnomad OTH exome AF: 0.000276

GnomAD4 exome AF: 0.000231 AC: 231 AN: 999325 Hom.: 2 Cov.: 23 AF XY: 0.000291 AC XY: 84 AN XY: 288329

Gnomad4 AFR exome AF: 0.000123

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00250

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000729

Gnomad4 OTH exome AF: 0.000211

GnomAD4 genome AF: 0.000350 AC: 33 AN: 94316 Hom.: 0 Cov.: 20 AF XY: 0.000263 AC XY: 8 AN XY: 30476

Gnomad4 AFR AF: 0.000213

Gnomad4 AMR AF: 0.000991

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00249

Gnomad4 SAS AF: 0.000413

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000209

Gnomad4 OTH AF: 0.000806

Alfa AF: 0.000269 Hom.: 1

Bravo AF: 0.000397

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Mar 12, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 01, 2018	- -

Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Benign:1

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Jun 19, 2019

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 27, 2019

- -

Duchenne muscular dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.51
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.011
dbscSNV1_RF	Benign	0.086
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

Publications

LitVar

Other links and lift over

dbSNP: rs3764764; hg19: chrX-32867946;