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rs978977375

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_004006.3(DMD):c.4105A>G(p.Ile1369Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000331 in 1,208,862 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD Genomes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

DMD
NM_004006.3 missense

Scores

1
2
9

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 3.65
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 Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.17813495).
BP6
Variant X-32411880-T-C is Benign according to our data. Variant chrX-32411880-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 526047.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DMDNM_004006.3 linkuse as main transcriptc.4105A>G p.Ile1369Val missense_variant 30/79 ENST00000357033.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DMDENST00000357033.9 linkuse as main transcriptc.4105A>G p.Ile1369Val missense_variant 30/791 NM_004006.3 P4

Frequencies

GnomAD3 genomes
AF:
0.00000898
AC:
1
AN:
111322
Hom.:
0
Cov.:
23
AF XY:
0.0000299
AC XY:
1
AN XY:
33500
show subpopulations
Gnomad AFR
AF:
0.0000327
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000547
AC:
1
AN:
182726
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67458
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
AF:
0.00000273
AC:
3
AN:
1097540
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
1
AN XY:
363018
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000238
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000898
AC:
1
AN:
111322
Hom.:
0
Cov.:
23
AF XY:
0.0000299
AC XY:
1
AN XY:
33500
show subpopulations
Gnomad4 AFR
AF:
0.0000327
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingNatera, Inc.Jul 25, 2019- -
Duchenne muscular dystrophy Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 23, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.76
Cadd
Benign
18
Dann
Benign
0.94
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.79
T;.;T;T
M_CAP
Pathogenic
0.36
D
MetaRNN
Benign
0.18
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.77
N;N
PrimateAI
Uncertain
0.59
T
Sift4G
Benign
0.72
T;T;T;T
Polyphen
0.13
.;B;.;.
Vest4
0.36
MutPred
0.37
.;.;Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP
0.49
MPC
0.026
ClinPred
0.18
T
GERP RS
5.7
gMVP
0.049

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: rs978977375; hg19: chrX-32429997; API