4-3493120-G-A

Position:

chr4-3493120-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173660.5(DOK7):c.1134G>A(p.Ala378=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,590,450 control chromosomes in the GnomAD database, including 38,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3380 hom., cov: 34)

Exomes 𝑓: 0.21 ( 34931 hom. )

Consequence

DOK7
NM_173660.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.09

Variant links:

Genes affected

DOK7 (HGNC:26594): (docking protein 7) The protein encoded by this gene is essential for neuromuscular synaptogenesis. The protein functions in aneural activation of muscle-specific receptor kinase, which is required for postsynaptic differentiation, and in the subsequent clustering of the acetylcholine receptor in myotubes. This protein can also induce autophosphorylation of muscle-specific receptor kinase. Mutations in this gene are a cause of familial limb-girdle myasthenia autosomal recessive, which is also known as congenital myasthenic syndrome type 1B. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

DOK7 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=-0.84).

BP6

Variant 4-3493120-G-A is Benign according to our data. Variant chr4-3493120-G-A is described in ClinVar as [Benign]. Clinvar id is 128905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3493120-G-A is described in Lovd as [Benign]. Variant chr4-3493120-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK7	NM_173660.5 linkuse as main transcript	c.1134G>A	p.Ala378=	synonymous_variant	7/7	ENST00000340083.6	NP_775931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6 linkuse as main transcript	c.1134G>A	p.Ala378=	synonymous_variant	7/7	1	NM_173660.5	ENSP00000344432	P1	Q18PE1-1
DOK7	ENST00000643608.1 linkuse as main transcript	c.702G>A	p.Ala234=	synonymous_variant	5/8			ENSP00000495701
DOK7	ENST00000515886.5 linkuse as main transcript	c.204G>A	p.Ala68=	synonymous_variant	4/4	2		ENSP00000492194
DOK7	ENST00000507039.5 linkuse as main transcript	c.*355G>A		3_prime_UTR_variant	7/7	2		ENSP00000423614		Q18PE1-4

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27667

AN:

152054

Hom.:

3385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.186

GnomAD3 exomes

AF:

0.222

AC:

45117

AN:

203522

Hom.:

5908

AF XY:

0.224

AC XY:

25117

AN XY:

112218

show subpopulations

Gnomad AFR exome

AF:

0.0533

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.490

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.378

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.210

AC:

302498

AN:

1438278

Hom.:

34931

Cov.:

113

AF XY:

0.211

AC XY:

150616

AN XY:

714238

show subpopulations

Gnomad4 AFR exome

AF:

0.0469

Gnomad4 AMR exome

AF:

0.140

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.505

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.378

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.210

GnomAD4 genome

AF:

0.182

AC:

27665

AN:

152172

Hom.:

3380

Cov.:

AF XY:

0.189

AC XY:

14091

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0538

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.511

Gnomad4 SAS

AF:

0.223

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.168

Hom.:

1030

Bravo

AF:

0.160

Asia WGS

AF:

0.363

AC:

1266

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 23, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 19, 2016	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. -

Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.27

DANN

Benign

0.77

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