9-110721711-G-C

Variant names:

• chr9-110721711-G-C
• rs10733579
• NM_005592.4:c.629-12540G>C

Variant summary

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

The NM_005592.4(MUSK):​c.629-12540G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,000 control chromosomes in the GnomAD database, including 37,918 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 0.70 (37918 hom., cov: 31)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUSK	NM_005592.4	c.629-12540G>C		intron_variant	Intron 5 of 14	ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.629-12540G>C		intron_variant	Intron 5 of 14	5	NM_005592.4	ENSP00000363571.4
MUSK	ENST00000416899.7	c.629-12540G>C		intron_variant	Intron 5 of 13	5		ENSP00000393608.3
MUSK	ENST00000189978.10	c.629-6977G>C		intron_variant	Intron 5 of 13	5		ENSP00000189978.6

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106799 AN: 151882 Hom.: 37901 Cov.: 31

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.703 AC: 106872 AN: 152000 Hom.: 37918 Cov.: 31 AF XY: 0.700 AC XY: 52019 AN XY: 74306

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.752

Alfa AF: 0.606 Hom.: 1701

Bravo AF: 0.706

Asia WGS AF: 0.704 AC: 2450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.36
DANN	Benign	0.34

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: rs10733579; hg19: chr9-113483991;