rs1940245

Positions:

• chr9-110760637-C-A
• chr9-110760637-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.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

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSK	NM_005592.4	c.914-1565C>A		intron_variant		ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.914-1565C>A		intron_variant		5	NM_005592.4	ENSP00000363571	P4
MUSK	ENST00000189978.10	c.944-1565C>A		intron_variant		5		ENSP00000189978
MUSK	ENST00000416899.7	c.914-1565C>A		intron_variant		5		ENSP00000393608	A1
MUSK	ENST00000634612.1	n.336-1565C>A		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.260

Alfa AF: 0.238 Hom.: 4839

Bravo AF: 0.237

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.37
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: rs1940245; hg19: chr9-113522917;