chr9-110804077-C-T

Variant names:

• chr9-110804077-C-T
• rs2821142
• NM_005592.4:c.*3089C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 9

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• fetal akinesia deformation sequence 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005592.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUSK	NM_005592.4	MANE Select	c.*3089C>T		3_prime_UTR	Exon 15 of 15	NP_005583.1	O15146-1
	MUSK	NM_001166280.2		c.*3089C>T		3_prime_UTR	Exon 14 of 14	NP_001159752.1	O15146-2
	MUSK	NM_001166281.2		c.*3089C>T		3_prime_UTR	Exon 13 of 13	NP_001159753.1	O15146-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUSK	ENST00000374448.9	TSL:5 MANE Select	c.*3089C>T		3_prime_UTR	Exon 15 of 15	ENSP00000363571.4	O15146-1

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

African (AFR) AF: 0.265 AC: 10994 AN: 41456

American (AMR) AF: 0.337 AC: 5159 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1813 AN: 3466

East Asian (EAS) AF: 0.109 AC: 563 AN: 5176

South Asian (SAS) AF: 0.271 AC: 1305 AN: 4818

European-Finnish (FIN) AF: 0.511 AC: 5394 AN: 10546

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30400 AN: 67884

Other (OTH) AF: 0.411 AC: 869 AN: 2112

Alfa AF: 0.415 Hom.: 29516

Bravo AF: 0.358

Asia WGS AF: 0.210 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.59
PhyloP100		-0.0020

Splicing

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

Other links and lift over

dbSNP: rs2821142; hg19: chr9-113566357;