Variant 9-110697488-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005592.4(MUSK):c.628+22C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 1,601,228 control chromosomes in the GnomAD database, including 2,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 272 hom., cov: 32)

Exomes 𝑓: 0.057 ( 2520 hom. )

Consequence

MUSK
NM_005592.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.164

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-110697488-C-G is Benign according to our data. Variant chr9-110697488-C-G is described in ClinVar as [Benign]. Clinvar id is 259811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0816 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.628+22C>G		intron_variant		ENST00000374448.9	NP_005583.1	O15146-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MUSK	ENST00000374448.9 linkuse as main transcript	c.628+22C>G	intron_variant	5	NM_005592.4	ENSP00000363571.4	O15146-1
MUSK	ENST00000416899.7 linkuse as main transcript	c.628+22C>G	intron_variant	5		ENSP00000393608.3	A0A087WSY1
MUSK	ENST00000189978.10 linkuse as main transcript	c.628+22C>G	intron_variant	5		ENSP00000189978.6	O15146-2
MUSK	ENST00000374439.1 linkuse as main transcript	c.322+22C>G	intron_variant	5		ENSP00000363562.2	F6XAJ2

Frequencies

GnomAD3 genomes

AF:

0.0568

AC:

8635

AN:

152054

Hom.:

271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0623

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0486

Gnomad ASJ

AF:

0.0681

Gnomad EAS

AF:

0.0881

Gnomad SAS

AF:

0.0723

Gnomad FIN

AF:

0.0226

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0569

Gnomad OTH

AF:

0.0574

GnomAD3 exomes

AF:

0.0583

AC:

14183

AN:

243184

Hom.:

497

AF XY:

0.0598

AC XY:

7897

AN XY:

132026

show subpopulations

Gnomad AFR exome

AF:

0.0649

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0636

Gnomad EAS exome

AF:

0.102

Gnomad SAS exome

AF:

0.0737

Gnomad FIN exome

AF:

0.0270

Gnomad NFE exome

AF:

0.0593

Gnomad OTH exome

AF:

0.0539

GnomAD4 exome

AF:

0.0571

AC:

82775

AN:

1449056

Hom.:

2520

Cov.:

AF XY:

0.0580

AC XY:

41748

AN XY:

720186

show subpopulations

Gnomad4 AFR exome

AF:

0.0635

Gnomad4 AMR exome

AF:

0.0366

Gnomad4 ASJ exome

AF:

0.0627

Gnomad4 EAS exome

AF:

0.0885

Gnomad4 SAS exome

AF:

0.0733

Gnomad4 FIN exome

AF:

0.0297

Gnomad4 NFE exome

AF:

0.0565

Gnomad4 OTH exome

AF:

0.0583

GnomAD4 genome

AF:

0.0568

AC:

8644

AN:

152172

Hom.:

272

Cov.:

AF XY:

0.0555

AC XY:

4128

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0624

Gnomad4 AMR

AF:

0.0486

Gnomad4 ASJ

AF:

0.0681

Gnomad4 EAS

AF:

0.0883

Gnomad4 SAS

AF:

0.0717

Gnomad4 FIN

AF:

0.0226

Gnomad4 NFE

AF:

0.0569

Gnomad4 OTH

AF:

0.0582

Alfa

AF:

0.0274

Hom.:

Bravo

AF:

0.0584

Asia WGS

AF:

0.0690

AC:

238

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

DANN

Benign

0.43

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