9-110740490-A-G

Position:

• chr9-110740490-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005592.4(MUSK):​c.753+6115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,102 control chromosomes in the GnomAD database, including 52,354 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (52354 hom., cov: 31)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSK	NM_005592.4	c.753+6115A>G		intron_variant		ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.753+6115A>G		intron_variant		5	NM_005592.4	ENSP00000363571.4
MUSK	ENST00000416899.7	c.753+6115A>G		intron_variant		5		ENSP00000393608.3
MUSK	ENST00000189978.10	c.783+6115A>G		intron_variant		5		ENSP00000189978.6
MUSK	ENST00000634612.1	n.175+6115A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125357 AN: 151984 Hom.: 52322 Cov.: 31

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.825

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.825 AC: 125444 AN: 152102 Hom.: 52354 Cov.: 31 AF XY: 0.822 AC XY: 61112 AN XY: 74334

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.821

Alfa AF: 0.799 Hom.: 7723

Bravo AF: 0.820

Asia WGS AF: 0.743 AC: 2587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	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: rs10817088; hg19: chr9-113502770;