rs128626236

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The ENST00000357033.9(DMD):​c.503C>A​(p.Ala168Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 22)

Consequence

DMD
ENST00000357033.9 missense

Scores

11
4
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 10.0
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.992
PP5
Variant X-32816495-G-T is Pathogenic according to our data. Variant chrX-32816495-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 11230.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-32816495-G-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DMDNM_004006.3 linkuse as main transcriptc.503C>A p.Ala168Asp missense_variant 6/79 ENST00000357033.9 NP_003997.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DMDENST00000357033.9 linkuse as main transcriptc.503C>A p.Ala168Asp missense_variant 6/791 NM_004006.3 ENSP00000354923 P4

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Becker muscular dystrophy Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 01, 1994- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.72
D
BayesDel_noAF
Pathogenic
0.80
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.88
.;D;.;.;D
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;.;D;D;D
M_CAP
Pathogenic
0.79
D
MetaRNN
Pathogenic
0.99
D;D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationTaster
Benign
1.0
A;A;A
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-4.4
.;D;.;D;D
REVEL
Pathogenic
0.95
Sift
Pathogenic
0.0
.;D;.;D;D
Sift4G
Uncertain
0.030
D;D;D;D;D
Polyphen
1.0
.;D;.;.;D
Vest4
0.98
MutPred
0.93
.;.;Gain of disorder (P = 0.187);Gain of disorder (P = 0.187);.;
MVP
1.0
MPC
0.13
ClinPred
1.0
D
GERP RS
5.5
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs128626236; hg19: chrX-32834612; API