Variant 9-110800329-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_005592.4(MUSK):c.1951A>C(p.Met651Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000208 in 1,610,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

MUSK
NM_005592.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 5.12

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038600177).

BP6

Variant 9-110800329-A-C is Benign according to our data. Variant chr9-110800329-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 570516.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSK	NM_005592.4 linkuse as main transcript	c.1951A>C	p.Met651Leu	missense_variant	15/15	ENST00000374448.9	NP_005583.1	O15146-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MUSK	ENST00000374448.9 linkuse as main transcript	c.1951A>C	p.Met651Leu	missense_variant	15/15	5	NM_005592.4	ENSP00000363571.4	O15146-1
MUSK	ENST00000416899.7 linkuse as main transcript	c.1927A>C	p.Met643Leu	missense_variant	14/14	5		ENSP00000393608.3	A0A087WSY1
MUSK	ENST00000189978.10 linkuse as main transcript	c.1693A>C	p.Met565Leu	missense_variant	14/14	5		ENSP00000189978.6	O15146-2

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000310

AC:

AN:

248074

Hom.:

AF XY:

0.000268

AC XY:

AN XY:

134500

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00219

Gnomad NFE exome

AF:

0.000223

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.000202

AC:

295

AN:

1458638

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

155

AN XY:

724998

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00264

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000263

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000271

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Sep 15, 2023

- -

Fetal akinesia deformation sequence 1;C4225368:Congenital myasthenic syndrome 9

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.37

T;.;.;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.81

T;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.039

T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-1.4

N;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.9

N;.;.;.

REVEL

Benign

0.26

Sift

Benign

0.24

T;.;.;.

Sift4G

Benign

0.56

T;T;T;T

Polyphen

0.92

P;.;.;.

Vest4

0.44

MutPred

0.47

Loss of methylation at K649 (P = 0.0859);.;.;.;

MVP

0.39

MPC

0.15

ClinPred

0.98

GERP RS

5.1

Varity_R

0.46

gMVP

0.57

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