chrX-31266835-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000378723.7(DMD):c.-6G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000541 in 1,204,289 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 202 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., 11 hem., cov: 22)

Exomes 𝑓: 0.00056 ( 0 hom. 191 hem. )

Consequence

DMD
ENST00000378723.7 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 0.744

Publications

0 publications found

Variant links:

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

DMD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BS2

High AC in GnomAd4 at 34 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3 link	c.9225-5819G>T		intron_variant	Intron 62 of 78	ENST00000357033.9	NP_003997.2	P11532

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9 link	c.9225-5819G>T		intron_variant	Intron 62 of 78	1	NM_004006.3	ENSP00000354923.3		A0A075B6G3

Frequencies

GnomAD3 genomes

AF:

0.000305

AC:

AN:

111311

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000936

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000624

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000340

AC:

AN:

167649

AF XY:

0.000354

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000702

Gnomad NFE exome

AF:

0.000766

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000565

AC:

617

AN:

1092934

Hom.:

Cov.:

AF XY:

0.000532

AC XY:

191

AN XY:

359350

show subpopulations

African (AFR)

AF:

0.0000761

AC:

AN:

26282

American (AMR)

AF:

0.00

AC:

AN:

34826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19285

East Asian (EAS)

AF:

0.00

AC:

AN:

29995

South Asian (SAS)

AF:

0.00

AC:

AN:

53208

European-Finnish (FIN)

AF:

0.000175

AC:

AN:

39905

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4114

European-Non Finnish (NFE)

AF:

0.000675

AC:

567

AN:

839534

Other (OTH)

AF:

0.000895

AC:

AN:

45785

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000305

AC:

AN:

111355

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

AN XY:

33707

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30636

American (AMR)

AF:

0.0000935

AC:

AN:

10699

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2639

East Asian (EAS)

AF:

0.00

AC:

AN:

3481

South Asian (SAS)

AF:

0.00

AC:

AN:

2644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.000624

AC:

AN:

52885

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000564

Hom.:

Bravo

AF:

0.000276

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 23, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant classified as Uncertain Significance - Favor Benign. -

DMD-related disorder

Benign:1

Mar 21, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.74

PromoterAI

-0.086

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over