rs10980531

Positions:

chr9-110695446-G-A

Variant summary

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

The NM_005592.4(MUSK):c.402G>A(p.Glu134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,535,178 control chromosomes in the GnomAD database, including 24,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2166 hom., cov: 33)

Exomes 𝑓: 0.18 ( 21936 hom. )

Consequence

MUSK
NM_005592.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.227

Variant links:

Genes affected

MUSK (HGNC:7525): (muscle associated receptor tyrosine kinase) This gene encodes a muscle-specific tyrosine kinase receptor. The encoded protein may play a role in clustering of the acetylcholine receptor in the postsynaptic neuromuscular junction. Mutations in this gene have been associated with congenital myasthenic syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Oct 2009]

MUSK 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=-0.52).

BP6

Variant 9-110695446-G-A is Benign according to our data. Variant chr9-110695446-G-A is described in ClinVar as [Benign]. Clinvar id is 129635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-110695446-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.227 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSK	NM_005592.4 linkuse as main transcript	c.402G>A	p.Glu134=	synonymous_variant	4/15	ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9 linkuse as main transcript	c.402G>A	p.Glu134=	synonymous_variant	4/15	5	NM_005592.4	ENSP00000363571	P4	O15146-1
MUSK	ENST00000416899.7 linkuse as main transcript	c.402G>A	p.Glu134=	synonymous_variant	4/14	5		ENSP00000393608	A1
MUSK	ENST00000189978.10 linkuse as main transcript	c.402G>A	p.Glu134=	synonymous_variant	4/14	5		ENSP00000189978		O15146-2
MUSK	ENST00000374439.1 linkuse as main transcript	c.96G>A	p.Glu32=	synonymous_variant	2/4	5		ENSP00000363562

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25184

AN:

151970

Hom.:

2163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.0758

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.159

AC:

27829

AN:

175058

Hom.:

2327

AF XY:

0.163

AC XY:

15162

AN XY:

92840

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.0848

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.212

Gnomad SAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.176

AC:

242898

AN:

1383090

Hom.:

21936

Cov.:

AF XY:

0.176

AC XY:

120764

AN XY:

684428

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.0927

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.166

AC:

25199

AN:

152088

Hom.:

2166

Cov.:

AF XY:

0.164

AC XY:

12180

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.214

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.161

Alfa

AF:

0.174

Hom.:

1205

Bravo

AF:

0.159

Asia WGS

AF:

0.185

AC:

640

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 27, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Fetal akinesia deformation sequence 1;C4225368:Congenital myasthenic syndrome 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Congenital myasthenic syndrome 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.1

DANN

Benign

0.49

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