chr9-110769305-T-C

Position:

• chr9-110769305-T-C

Variant summary

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

The NM_005592.4(MUSK):​c.1184+1222T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,120 control chromosomes in the GnomAD database, including 52,391 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 0.83 (52391 hom., cov: 32)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSK	NM_005592.4	c.1184+1222T>C		intron_variant		ENST00000374448.9	NP_005583.1
LOC107987115	XR_001746892.2	n.258-4468A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.1184+1222T>C		intron_variant		5	NM_005592.4	ENSP00000363571	P4
MUSK	ENST00000189978.10	c.951-6483T>C		intron_variant		5		ENSP00000189978
MUSK	ENST00000416899.7	c.1184+1222T>C		intron_variant		5		ENSP00000393608	A1

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125868 AN: 152002 Hom.: 52348 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.828 AC: 125973 AN: 152120 Hom.: 52391 Cov.: 32 AF XY: 0.826 AC XY: 61461 AN XY: 74376

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.812

Alfa AF: 0.810 Hom.: 101171

Bravo AF: 0.827

Asia WGS AF: 0.752 AC: 2610 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.29
DANN	Benign	0.48

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: rs2766998; hg19: chr9-113531585; COSMIC: COSV51881627; COSMIC: COSV51881627;