9-110784973-C-T

Position:

• chr9-110784973-C-T

Variant summary

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

The NM_005592.4(MUSK):​c.1543C>T​(p.Leu515Phe) 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. 13/21 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: 33)
• Consequence: MUSK NM_005592.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15

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]

LOC107987115 (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=0.32511568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSK	NM_005592.4	c.1543C>T	p.Leu515Phe	missense_variant	12/15	ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.1543C>T	p.Leu515Phe	missense_variant	12/15	5	NM_005592.4	ENSP00000363571.4
MUSK	ENST00000416899.7	c.1519C>T	p.Leu507Phe	missense_variant	11/14	5		ENSP00000393608.3
MUSK	ENST00000189978.10	c.1285C>T	p.Leu429Phe	missense_variant	11/14	5		ENSP00000189978.6
MUSK	ENST00000374438.1	n.618-554C>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0027	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T;.;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.028
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.0	N;N;.;.
REVEL	Benign	0.26
Sift	Benign	0.27	T;T;.;.
Sift4G	Benign	0.080	T;T;T;T
Polyphen		0.0050	B;.;.;.
Vest4		0.43
MutPred		0.39		Gain of MoRF binding (P = 0.1399);.;.;.;
MVP		0.88
MPC		0.18
ClinPred		0.63	D
GERP RS		4.7
Varity_R		0.13
gMVP		0.39

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: rs1554755295; hg19: chr9-113547253;