Variant chr9-110682828-A-T 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.206+28A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,577,430 control chromosomes in the GnomAD database, including 9,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 702 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9016 hom. )

Consequence

MUSK
NM_005592.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.66

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=-0.89).

BP6

Variant 9-110682828-A-T is Benign according to our data. Variant chr9-110682828-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 259807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-110682828-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 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.206+28A>T		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.206+28A>T	intron_variant	5	NM_005592.4	ENSP00000363571.4	O15146-1
MUSK	ENST00000416899.7 linkuse as main transcript	c.206+28A>T	intron_variant	5		ENSP00000393608.3	A0A087WSY1
MUSK	ENST00000189978.10 linkuse as main transcript	c.206+28A>T	intron_variant	5		ENSP00000189978.6	O15146-2

Frequencies

GnomAD3 genomes

AF:

0.0881

AC:

13377

AN:

151810

Hom.:

702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0434

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0752

Gnomad ASJ

AF:

0.0684

Gnomad EAS

AF:

0.00790

Gnomad SAS

AF:

0.0520

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.0864

GnomAD3 exomes

AF:

0.0881

AC:

19925

AN:

226282

Hom.:

1114

AF XY:

0.0892

AC XY:

10980

AN XY:

123040

show subpopulations

Gnomad AFR exome

AF:

0.0465

Gnomad AMR exome

AF:

0.0454

Gnomad ASJ exome

AF:

0.0627

Gnomad EAS exome

AF:

0.00829

Gnomad SAS exome

AF:

0.0549

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.0947

GnomAD4 exome

AF:

0.108

AC:

153284

AN:

1425502

Hom.:

9016

Cov.:

AF XY:

0.106

AC XY:

75397

AN XY:

709932

show subpopulations

Gnomad4 AFR exome

AF:

0.0391

Gnomad4 AMR exome

AF:

0.0486

Gnomad4 ASJ exome

AF:

0.0626

Gnomad4 EAS exome

AF:

0.0117

Gnomad4 SAS exome

AF:

0.0534

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.0938

GnomAD4 genome

AF:

0.0881

AC:

13382

AN:

151928

Hom.:

702

Cov.:

AF XY:

0.0865

AC XY:

6422

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0435

Gnomad4 AMR

AF:

0.0751

Gnomad4 ASJ

AF:

0.0684

Gnomad4 EAS

AF:

0.00773

Gnomad4 SAS

AF:

0.0519

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.0859

Alfa

AF:

0.103

Hom.:

173

Bravo

AF:

0.0793

Asia WGS

AF:

0.0360

AC:

123

AN:

3478

ClinVar

Significance: Benign/Likely 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	Aug 07, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely 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

-0.89

CADD

Benign

0.19

DANN

Benign

0.29

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