9-110711886-G-C

Variant summary

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

The NM_005592.4(MUSK):c.628+14420G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,044 control chromosomes in the GnomAD database, including 25,381 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 0.57 (25381 hom., cov: 32)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUSK	NM_005592.4	c.628+14420G>C		intron_variant		ENST00000374448.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUSK	ENST00000374448.9	c.628+14420G>C		intron_variant		5	NM_005592.4	P4
MUSK	ENST00000189978.10	c.628+14420G>C		intron_variant		5
MUSK	ENST00000416899.7	c.628+14420G>C		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86001 AN: 151926 Hom.: 25369 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.566 AC: 86055 AN: 152044 Hom.: 25381 Cov.: 32 AF XY: 0.563 AC XY: 41867 AN XY: 74308

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.559

Alfa AF: 0.513 Hom.: 1645

Bravo AF: 0.540

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.32
Dann	Benign	0.41

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: rs10817082; hg19: chr9-113474166; COSMIC: COSV51881555;