rs72466570

Positions:

chrX-31479080-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004006.3(DMD):c.8571T>C(p.Thr2857Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,208,177 control chromosomes in the GnomAD database, including 3 homozygotes. There are 593 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 0.0015 ( 2 hom., 44 hem., cov: 23)

Exomes 𝑓: 0.0014 ( 1 hom. 549 hem. )

Consequence

DMD
NM_004006.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.151

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant X-31479080-A-G is Benign according to our data. Variant chrX-31479080-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 94809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-31479080-A-G is described in Lovd as [Benign]. Variant chrX-31479080-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.151 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0015 (167/111650) while in subpopulation NFE AF= 0.00229 (122/53163). AF 95% confidence interval is 0.00196. There are 2 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3 link	c.8571T>C	p.Thr2857Thr	synonymous_variant	58/79	ENST00000357033.9	NP_003997.2	P11532

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9 link	c.8571T>C	p.Thr2857Thr	synonymous_variant	58/79	1	NM_004006.3	ENSP00000354923.3		A0A075B6G3

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

167

AN:

111597

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

33777

show subpopulations

Gnomad AFR

AF:

0.000358

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000861

Gnomad ASJ

AF:

0.00793

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000167

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00199

GnomAD3 exomes

AF:

0.00151

AC:

277

AN:

182856

Hom.:

AF XY:

0.00159

AC XY:

107

AN XY:

67382

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.000548

Gnomad ASJ exome

AF:

0.00670

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000527

Gnomad FIN exome

AF:

0.00113

Gnomad NFE exome

AF:

0.00219

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00144

AC:

1579

AN:

1096527

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

549

AN XY:

361949

show subpopulations

Gnomad4 AFR exome

AF:

0.000303

Gnomad4 AMR exome

AF:

0.000881

Gnomad4 ASJ exome

AF:

0.00558

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.000938

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.00150

AC:

167

AN:

111650

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

33840

show subpopulations

Gnomad4 AFR

AF:

0.000358

Gnomad4 AMR

AF:

0.000860

Gnomad4 ASJ

AF:

0.00793

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000167

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.00197

Alfa

AF:

0.00345

Hom.:

Bravo

AF:

0.00129

EpiCase

AF:

0.00245

EpiControl

AF:

0.00226

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 04, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 18, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 02, 2013	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Oct 16, 2017

- -

Dilated cardiomyopathy 3B

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

DMD-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 16, 2020

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). -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2016

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.6

DANN

Benign

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over