rs752129019

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004006.3(DMD):​c.4409G>T​(p.Arg1470Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 111,405 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Consequence

DMD
NM_004006.3 missense

Scores

5
9
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.71
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DMDNM_004006.3 linkuse as main transcriptc.4409G>T p.Arg1470Leu missense_variant 32/79 ENST00000357033.9 NP_003997.2 P11532

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DMDENST00000357033.9 linkuse as main transcriptc.4409G>T p.Arg1470Leu missense_variant 32/791 NM_004006.3 ENSP00000354923.3 A0A075B6G3

Frequencies

GnomAD3 genomes
AF:
0.00000898
AC:
1
AN:
111405
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33641
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000189
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000547
AC:
1
AN:
182821
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67513
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000898
AC:
1
AN:
111405
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33641
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000189
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
.;T;.;.
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;.;D;D
M_CAP
Pathogenic
0.75
D
MetaRNN
Pathogenic
0.76
D;D;D;D
MetaSVM
Benign
-0.86
T
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-5.2
.;D;.;D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0020
.;D;.;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.78
MutPred
0.46
.;.;Loss of MoRF binding (P = 0.0189);Loss of MoRF binding (P = 0.0189);
MVP
0.80
MPC
0.084
ClinPred
1.0
D
GERP RS
5.6
gMVP
0.69

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.

Other links and lift over

dbSNP: rs752129019; hg19: chrX-32407727; API