chrX-32485077-T-C

Position:

chrX-32485077-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_004006.3(DMD):c.2645A>G(p.Asp882Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.68 ( 18016 hom., 22248 hem., cov: 23)

Exomes 𝑓: 0.68 ( 171444 hom. 248464 hem. )

Failed GnomAD Quality Control

Consequence

DMD
NM_004006.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.937

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:

DMD (HGNC:):

DMD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8961167E-5).

BP6

Variant X-32485077-T-C is Benign according to our data. Variant chrX-32485077-T-C is described in ClinVar as [Benign]. Clinvar id is 166842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-32485077-T-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3 linkuse as main transcript	c.2645A>G	p.Asp882Gly	missense_variant	21/79	ENST00000357033.9	NP_003997.2	P11532

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9 linkuse as main transcript	c.2645A>G	p.Asp882Gly	missense_variant	21/79	1	NM_004006.3	ENSP00000354923.3		A0A075B6G3

Frequencies

GnomAD3 genomes

AF:

0.679

AC:

74818

AN:

110201

Hom.:

18029

Cov.:

AF XY:

0.684

AC XY:

22212

AN XY:

32453

show subpopulations

Gnomad AFR

AF:

0.630

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.764

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.874

Gnomad SAS

AF:

0.789

Gnomad FIN

AF:

0.813

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.661

Gnomad OTH

AF:

0.687

GnomAD3 exomes

AF:

0.728

AC:

133392

AN:

183171

Hom.:

31450

AF XY:

0.724

AC XY:

48969

AN XY:

67641

show subpopulations

Gnomad AFR exome

AF:

0.626

Gnomad AMR exome

AF:

0.854

Gnomad ASJ exome

AF:

0.610

Gnomad EAS exome

AF:

0.886

Gnomad SAS exome

AF:

0.780

Gnomad FIN exome

AF:

0.812

Gnomad NFE exome

AF:

0.660

Gnomad OTH exome

AF:

0.699

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.682

AC:

748068

AN:

1097332

Hom.:

171444

Cov.:

AF XY:

0.684

AC XY:

248464

AN XY:

363044

show subpopulations

Gnomad4 AFR exome

AF:

0.626

Gnomad4 AMR exome

AF:

0.844

Gnomad4 ASJ exome

AF:

0.616

Gnomad4 EAS exome

AF:

0.854

Gnomad4 SAS exome

AF:

0.780

Gnomad4 FIN exome

AF:

0.805

Gnomad4 NFE exome

AF:

0.659

Gnomad4 OTH exome

AF:

0.686

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.679

AC:

74834

AN:

110252

Hom.:

18016

Cov.:

AF XY:

0.684

AC XY:

22248

AN XY:

32514

show subpopulations

Gnomad4 AFR

AF:

0.630

Gnomad4 AMR

AF:

0.765

Gnomad4 ASJ

AF:

0.615

Gnomad4 EAS

AF:

0.875

Gnomad4 SAS

AF:

0.789

Gnomad4 FIN

AF:

0.813

Gnomad4 NFE

AF:

0.661

Gnomad4 OTH

AF:

0.679

Alfa

AF:

0.661

Hom.:

85314

Bravo

AF:

0.679

TwinsUK

AF:

0.664

AC:

2463

ALSPAC

AF:

0.652

AC:

1883

ESP6500AA

AF:

0.628

AC:

2407

ESP6500EA

AF:

0.663

AC:

4460

ExAC

AF:

0.719

AC:

87334

EpiCase

AF:

0.659

EpiControl

AF:

0.654

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 04, 2016	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 26, 2014	This is a RefSeq error. The reference base (c.2645A) is the minor allele. This a llele (A) has been identified in 34% (2268/6728) of European American chromosome s and 37% (1426/3833) of African American chromosomes by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs228406) and thus meets c riteria to be classified as benign. -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2019	This variant is associated with the following publications: (PMID: 30342905, 29604111) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Duchenne muscular dystrophy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

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

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 20, 2017

- -

Dilated cardiomyopathy 3B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.89

BayesDel_noAF

Benign

-0.90

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.20

.;T;.;.

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.015

T;.;T;T

MetaRNN

Benign

0.000019

T;T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.28

PROVEAN

Benign

0.45

.;N;.;N

REVEL

Benign

0.022

Sift

Benign

0.52

.;T;.;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0

.;B;.;.

Vest4

0.056

MPC

0.016

ClinPred

0.0016

GERP RS

3.1

gMVP

0.14

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