rs10980564

chr9-110770170-G-Achr9-110770170-G-T

Variant summary

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

The NM_005592.4(MUSK):c.1184+2087G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 150,306 control chromosomes in the GnomAD database, including 12,078 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 0.39 (12078 hom., cov: 31)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUSK	NM_005592.4	c.1184+2087G>A		intron_variant		ENST00000374448.9
LOC107987115	XR_001746892.2	n.258-5333C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUSK	ENST00000374448.9	c.1184+2087G>A		intron_variant		5	NM_005592.4	P4
MUSK	ENST00000189978.10	c.951-5618G>A		intron_variant		5
MUSK	ENST00000416899.7	c.1184+2087G>A		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58058 AN: 150196 Hom.: 12076 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.0894

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.386 AC: 58077 AN: 150306 Hom.: 12078 Cov.: 31 AF XY: 0.384 AC XY: 28194 AN XY: 73358

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.0892

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.418

Alfa AF: 0.323 Hom.: 1518

Bravo AF: 0.371

Asia WGS AF: 0.191 AC: 663 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.4
Dann	Benign	0.59

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: rs10980564; hg19: chr9-113532450;