rs79843573

Positions:

• chr9-110775792-T-A
• chr9-110775792-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005592.4(MUSK):​c.1189T>A​(p.Tyr397Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MUSK NM_005592.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.34

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39807266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSK	NM_005592.4	c.1189T>A	p.Tyr397Asn	missense_variant	10/15	ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.1189T>A	p.Tyr397Asn	missense_variant	10/15	5	NM_005592.4	ENSP00000363571.4
MUSK	ENST00000416899.7	c.1189T>A	p.Tyr397Asn	missense_variant	10/14	5		ENSP00000393608.3
MUSK	ENST00000189978.10	c.955T>A	p.Tyr319Asn	missense_variant	10/14	5		ENSP00000189978.6
MUSK	ENST00000374438.1	n.446T>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.069	T;.;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.55	N;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.56	N;.;.;.
REVEL	Uncertain	0.33
Sift	Benign	0.67	T;.;.;.
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.78	P;.;.;.
Vest4		0.11
MutPred		0.62		Loss of methylation at K402 (P = 0.0473);Loss of methylation at K402 (P = 0.0473);.;.;
MVP		0.80
MPC		0.49
ClinPred		0.89	D
GERP RS		4.3
Varity_R		0.085
gMVP		0.79

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

Other links and lift over

dbSNP: rs79843573; hg19: chr9-113538072;