Variant 9-110787888-T-C 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.1927+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,563,634 control chromosomes in the GnomAD database, including 172,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17382 hom., cov: 31)

Exomes 𝑓: 0.46 ( 154802 hom. )

Consequence

MUSK
NM_005592.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.220

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=-0.78).

BP6

Variant 9-110787888-T-C is Benign according to our data. Variant chr9-110787888-T-C is described in ClinVar as [Benign]. Clinvar id is 259804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-110787888-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 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.1927+50T>C		intron_variant		ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9 linkuse as main transcript	c.1927+50T>C	intron_variant		5	NM_005592.4	ENSP00000363571	P4	O15146-1
MUSK	ENST00000189978.10 linkuse as main transcript	c.1669+50T>C	intron_variant		5		ENSP00000189978		O15146-2
MUSK	ENST00000416899.7 linkuse as main transcript	c.1903+50T>C	intron_variant		5		ENSP00000393608	A1
MUSK	ENST00000374438.1 linkuse as main transcript	n.1008T>C	non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71492

AN:

151854

Hom.:

17362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.521

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.496

GnomAD3 exomes

AF:

0.425

AC:

77509

AN:

182458

Hom.:

17705

AF XY:

0.427

AC XY:

41253

AN XY:

96670

show subpopulations

Gnomad AFR exome

AF:

0.515

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.583

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.358

Gnomad FIN exome

AF:

0.514

Gnomad NFE exome

AF:

0.483

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.462

AC:

652097

AN:

1411662

Hom.:

154802

Cov.:

AF XY:

0.459

AC XY:

320555

AN XY:

698290

show subpopulations

Gnomad4 AFR exome

AF:

0.523

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.583

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.353

Gnomad4 FIN exome

AF:

0.511

Gnomad4 NFE exome

AF:

0.478

Gnomad4 OTH exome

AF:

0.468

GnomAD4 genome

AF:

0.471

AC:

71563

AN:

151972

Hom.:

17382

Cov.:

AF XY:

0.470

AC XY:

34945

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.518

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.126

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.521

Gnomad4 NFE

AF:

0.482

Gnomad4 OTH

AF:

0.495

Alfa

AF:

0.455

Hom.:

4458

Bravo

AF:

0.464

Asia WGS

AF:

0.253

AC:

885

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

-0.78

CADD

Benign

6.7

DANN

Benign

0.53

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