rs12690372

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004006.3(DMD):​c.9804A>G​(p.Gln3268Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,204,139 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 9 hem., cov: 24)
Exomes 𝑓: 0.000088 ( 0 hom. 31 hem. )

Consequence

DMD
NM_004006.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.200

Publications

1 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6
Variant X-31203964-T-C is Benign according to our data. Variant chrX-31203964-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 94861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000879 (96/1091871) while in subpopulation EAS AF = 0.00239 (72/30176). AF 95% confidence interval is 0.00194. There are 0 homozygotes in GnomAdExome4. There are 31 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.
BS2
High AC in GnomAd4 at 28 XL,AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DMDNM_004006.3 linkc.9804A>G p.Gln3268Gln synonymous_variant Exon 67 of 79 ENST00000357033.9 NP_003997.2 P11532

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DMDENST00000357033.9 linkc.9804A>G p.Gln3268Gln synonymous_variant Exon 67 of 79 1 NM_004006.3 ENSP00000354923.3 A0A075B6G3

Frequencies

GnomAD3 genomes
AF:
0.000249
AC:
28
AN:
112268
Hom.:
0
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.000811
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000558
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000657
GnomAD2 exomes
AF:
0.000300
AC:
55
AN:
183250
AF XY:
0.000266
show subpopulations
Gnomad AFR exome
AF:
0.000684
Gnomad AMR exome
AF:
0.0000730
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00304
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000879
AC:
96
AN:
1091871
Hom.:
0
Cov.:
29
AF XY:
0.0000867
AC XY:
31
AN XY:
357465
show subpopulations
African (AFR)
AF:
0.000495
AC:
13
AN:
26283
American (AMR)
AF:
0.0000568
AC:
2
AN:
35199
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19338
East Asian (EAS)
AF:
0.00239
AC:
72
AN:
30176
South Asian (SAS)
AF:
0.0000371
AC:
2
AN:
53977
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40531
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4127
European-Non Finnish (NFE)
AF:
0.00000239
AC:
2
AN:
836336
Other (OTH)
AF:
0.000109
AC:
5
AN:
45904
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
5
10
16
21
26
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<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:
0.000249
AC:
28
AN:
112268
Hom.:
0
Cov.:
24
AF XY:
0.000261
AC XY:
9
AN XY:
34428
show subpopulations
African (AFR)
AF:
0.000811
AC:
25
AN:
30834
American (AMR)
AF:
0.00
AC:
0
AN:
10628
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2651
East Asian (EAS)
AF:
0.000558
AC:
2
AN:
3584
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2700
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6118
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
240
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
53305
Other (OTH)
AF:
0.000657
AC:
1
AN:
1521
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.512
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
2
4
6
8
10
<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:
0.000142
Hom.:
0
Bravo
AF:
0.000291

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Aug 14, 2015
Eurofins Ntd Llc (ga)
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Benign:1
May 20, 2019
Natera, Inc.
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

not provided Benign:1
Nov 14, 2020
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Cardiovascular phenotype Benign:1
Mar 11, 2015
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Duchenne muscular dystrophy Benign:1
Jan 26, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
7.8
DANN
Benign
0.34
PhyloP100
0.20
Mutation Taster
=98/2
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.37
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.37
Position offset: -23

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

Publications

Other links and lift over

dbSNP: rs12690372; hg19: chrX-31222081; API