chrX-32849823-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_004006.3(DMD):c.94-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,159,892 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000021 ( 0 hom. 5 hem. )

Consequence

DMD
NM_004006.3 splice_region, intron

Scores

Splicing: ADA: 0.03960

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 2.56

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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant X-32849823-G-A is Benign according to our data. Variant chrX-32849823-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 196374.

BS2

High AC in GnomAd4 at 17 XL,AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DMD	NM_004006.3	MANE Select	c.94-3C>T	splice_region intron	N/A	NP_003997.2
DMD	NM_004009.3		c.82-3C>T	splice_region intron	N/A	NP_004000.1
DMD	NM_000109.4		c.70-3C>T	splice_region intron	N/A	NP_000100.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DMD	ENST00000357033.9	TSL:1 MANE Select	c.94-3C>T	splice_region intron	N/A	ENSP00000354923.3
DMD	ENST00000288447.9	TSL:1	c.70-3C>T	splice_region intron	N/A	ENSP00000288447.4
DMD	ENST00000378677.6	TSL:5	c.82-3C>T	splice_region intron	N/A	ENSP00000367948.2

Frequencies

GnomAD3 genomes

AF:

0.000159

AC:

AN:

106677

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000568

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000457

AC:

AN:

175231

AF XY:

0.0000165

show subpopulations

Gnomad AFR exome

AF:

0.000540

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000233

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1053215

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

322655

show subpopulations

African (AFR)

AF:

0.000742

AC:

AN:

25601

American (AMR)

AF:

0.00

AC:

AN:

34983

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18996

East Asian (EAS)

AF:

0.00

AC:

AN:

29950

South Asian (SAS)

AF:

0.00

AC:

AN:

52843

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40422

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4013

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

801842

Other (OTH)

AF:

0.0000673

AC:

AN:

44565

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000159

AC:

AN:

106677

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

29997

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

29925

American (AMR)

AF:

0.00

AC:

AN:

9966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2434

East Asian (EAS)

AF:

0.00

AC:

AN:

3288

South Asian (SAS)

AF:

0.00

AC:

AN:

2516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5459

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50876

Other (OTH)

AF:

0.00

AC:

AN:

1398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

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:

0.000219

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Cardiovascular phenotype (1)

DMD-related disorder (1)

Duchenne muscular dystrophy (1)

Dystrophin deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

2.6

PromoterAI

-0.028

Neutral

(source)

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.040

dbscSNV1_RF

Benign

0.11

Splicevardb

2.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over