chr9-110697375-C-T

Position:

chr9-110697375-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005592.4(MUSK):c.537C>T(p.Asn179=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,610,998 control chromosomes in the GnomAD database, including 25,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1786 hom., cov: 31)

Exomes 𝑓: 0.18 ( 23880 hom. )

Consequence

MUSK
NM_005592.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0990

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 9-110697375-C-T is Benign according to our data. Variant chr9-110697375-C-T is described in ClinVar as [Benign]. Clinvar id is 129637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-110697375-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.099 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 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.537C>T	p.Asn179=	synonymous_variant	5/15	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.537C>T	p.Asn179=	synonymous_variant	5/15	5	NM_005592.4	ENSP00000363571	P4	O15146-1
MUSK	ENST00000416899.7 linkuse as main transcript	c.537C>T	p.Asn179=	synonymous_variant	5/14	5		ENSP00000393608	A1
MUSK	ENST00000189978.10 linkuse as main transcript	c.537C>T	p.Asn179=	synonymous_variant	5/14	5		ENSP00000189978		O15146-2
MUSK	ENST00000374439.1 linkuse as main transcript	c.231C>T	p.Asn77=	synonymous_variant	3/4	5		ENSP00000363562

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20532

AN:

151848

Hom.:

1780

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0302

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.0894

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.109

GnomAD3 exomes

AF:

0.161

AC:

39982

AN:

248244

Hom.:

3717

AF XY:

0.167

AC XY:

22430

AN XY:

134710

show subpopulations

Gnomad AFR exome

AF:

0.0262

Gnomad AMR exome

AF:

0.0661

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.194

Gnomad SAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.253

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.177

AC:

258273

AN:

1459032

Hom.:

23880

Cov.:

AF XY:

0.178

AC XY:

129126

AN XY:

725780

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

Gnomad4 AMR exome

AF:

0.0695

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.246

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.135

AC:

20542

AN:

151966

Hom.:

1786

Cov.:

AF XY:

0.139

AC XY:

10297

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0301

Gnomad4 AMR

AF:

0.0891

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.175

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.157

Hom.:

1103

Bravo

AF:

0.117

Asia WGS

AF:

0.163

AC:

568

AN:

3478

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	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. -

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

-0.32

CADD

Benign

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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