rs1940245

Variant names:

• chr9-110760637-C-A
• rs1940245
• NM_005592.4:c.914-1565C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-110760637-C-A
• chr9-110760637-C-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.914-1565C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,740 control chromosomes in the GnomAD database, including 4,224 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 0.23 (4224 hom., cov: 31)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 8 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), PanelApp Australia
• fetal akinesia deformation sequence 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUSK	NM_005592.4	MANE Select	c.914-1565C>A		intron	N/A	NP_005583.1
	MUSK	NM_001166280.2		c.944-1565C>A		intron	N/A	NP_001159752.1
	MUSK	NM_001166281.2		c.914-1565C>A		intron	N/A	NP_001159753.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUSK	ENST00000374448.9	TSL:5 MANE Select	c.914-1565C>A		intron	N/A	ENSP00000363571.4
	MUSK	ENST00000416899.7	TSL:5	c.914-1565C>A		intron	N/A	ENSP00000393608.3
	MUSK	ENST00000189978.10	TSL:5	c.944-1565C>A		intron	N/A	ENSP00000189978.6

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34852 AN: 151628 Hom.: 4222 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.230 AC: 34865 AN: 151740 Hom.: 4224 Cov.: 31 AF XY: 0.230 AC XY: 17023 AN XY: 74114

African (AFR) AF: 0.187 AC: 7744 AN: 41350

American (AMR) AF: 0.269 AC: 4104 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3470

East Asian (EAS) AF: 0.355 AC: 1834 AN: 5162

South Asian (SAS) AF: 0.243 AC: 1165 AN: 4802

European-Finnish (FIN) AF: 0.168 AC: 1757 AN: 10484

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16264 AN: 67932

Other (OTH) AF: 0.260 AC: 546 AN: 2096

Alfa AF: 0.239 Hom.: 7061

Bravo AF: 0.237

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.37
DANN	Benign	0.48
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1940245; hg19: chr9-113522917;