rs2821142

Positions:

• chr9-110804077-C-T

Variant summary

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

The NM_005592.4(MUSK):​c.*3089C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,954 control chromosomes in the GnomAD database, including 11,477 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 0.37 (11477 hom., cov: 32)
• Consequence: MUSK NM_005592.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSK	NM_005592.4	c.*3089C>T		3_prime_UTR_variant	15/15	ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.*3089C>T		3_prime_UTR_variant	15/15	5	NM_005592.4	ENSP00000363571.4

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56923 AN: 151836 Hom.: 11469 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.375 AC: 56956 AN: 151954 Hom.: 11477 Cov.: 32 AF XY: 0.378 AC XY: 28048 AN XY: 74270

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.411

Alfa AF: 0.427 Hom.: 20129

Bravo AF: 0.358

Asia WGS AF: 0.210 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2821142; hg19: chr9-113566357;