Variant rs71501643 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.207-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 1,601,560 control chromosomes in the GnomAD database, including 2,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 217 hom., cov: 31)

Exomes 𝑓: 0.056 ( 2411 hom. )

Consequence

MUSK
NM_005592.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.404

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=-0.83).

BP6

Variant 9-110687097-T-C is Benign according to our data. Variant chr9-110687097-T-C is described in ClinVar as [Benign]. Clinvar id is 259808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0827 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.207-20T>C		intron_variant		ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9 linkuse as main transcript	c.207-20T>C	intron_variant	5	NM_005592.4	ENSP00000363571	P4	O15146-1
MUSK	ENST00000189978.10 linkuse as main transcript	c.207-20T>C	intron_variant	5		ENSP00000189978		O15146-2
MUSK	ENST00000416899.7 linkuse as main transcript	c.207-20T>C	intron_variant	5		ENSP00000393608	A1

Frequencies

GnomAD3 genomes

AF:

0.0483

AC:

7341

AN:

152014

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0320

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0471

Gnomad ASJ

AF:

0.0677

Gnomad EAS

AF:

0.0892

Gnomad SAS

AF:

0.0636

Gnomad FIN

AF:

0.0222

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0574

Gnomad OTH

AF:

0.0549

GnomAD3 exomes

AF:

0.0553

AC:

13427

AN:

242596

Hom.:

439

AF XY:

0.0566

AC XY:

7447

AN XY:

131492

show subpopulations

Gnomad AFR exome

AF:

0.0351

Gnomad AMR exome

AF:

0.0337

Gnomad ASJ exome

AF:

0.0653

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.0646

Gnomad FIN exome

AF:

0.0271

Gnomad NFE exome

AF:

0.0595

Gnomad OTH exome

AF:

0.0531

GnomAD4 exome

AF:

0.0560

AC:

81108

AN:

1449428

Hom.:

2411

Cov.:

AF XY:

0.0566

AC XY:

40695

AN XY:

719616

show subpopulations

Gnomad4 AFR exome

AF:

0.0329

Gnomad4 AMR exome

AF:

0.0358

Gnomad4 ASJ exome

AF:

0.0629

Gnomad4 EAS exome

AF:

0.0860

Gnomad4 SAS exome

AF:

0.0644

Gnomad4 FIN exome

AF:

0.0296

Gnomad4 NFE exome

AF:

0.0568

Gnomad4 OTH exome

AF:

0.0559

GnomAD4 genome

AF:

0.0483

AC:

7341

AN:

152132

Hom.:

217

Cov.:

AF XY:

0.0473

AC XY:

3517

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0319

Gnomad4 AMR

AF:

0.0471

Gnomad4 ASJ

AF:

0.0677

Gnomad4 EAS

AF:

0.0894

Gnomad4 SAS

AF:

0.0631

Gnomad4 FIN

AF:

0.0222

Gnomad4 NFE

AF:

0.0574

Gnomad4 OTH

AF:

0.0562

Alfa

AF:

0.0503

Hom.:

Bravo

AF:

0.0496

Asia WGS

AF:

0.0670

AC:

231

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.5

DANN

Benign

0.66

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