rs4524871

Positions:

• chr9-110700728-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+3262G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,100 control chromosomes in the GnomAD database, including 1,820 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 0.14 (1820 hom., cov: 32)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUSK	NM_005592.4	c.628+3262G>C		intron_variant		ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.628+3262G>C		intron_variant		5	NM_005592.4	ENSP00000363571.4
MUSK	ENST00000416899.7	c.628+3262G>C		intron_variant		5		ENSP00000393608.3
MUSK	ENST00000189978.10	c.628+3262G>C		intron_variant		5		ENSP00000189978.6
MUSK	ENST00000374439.1	c.322+3262G>C		intron_variant		5		ENSP00000363562.2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21129 AN: 151982 Hom.: 1814 Cov.: 32

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.139 AC: 21140 AN: 152100 Hom.: 1820 Cov.: 32 AF XY: 0.143 AC XY: 10619 AN XY: 74360

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.0920

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.116

Alfa AF: 0.158 Hom.: 258

Bravo AF: 0.121

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.61

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: rs4524871; hg19: chr9-113463008;