rs3010815

Variant names:

• chr9-110671898-C-T
• rs3010815
• NM_005592.4:c.79+2915C>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.79+2915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,052 control chromosomes in the GnomAD database, including 23,060 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 0.54 (23060 hom., cov: 33)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUSK	NM_005592.4	c.79+2915C>T		intron_variant	Intron 1 of 14	ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.79+2915C>T		intron_variant	Intron 1 of 14	5	NM_005592.4	ENSP00000363571.4
MUSK	ENST00000416899.7	c.79+2915C>T		intron_variant	Intron 1 of 13	5		ENSP00000393608.3
MUSK	ENST00000189978.10	c.79+2915C>T		intron_variant	Intron 1 of 13	5		ENSP00000189978.6

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81856 AN: 151934 Hom.: 23031 Cov.: 33

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.539 AC: 81925 AN: 152052 Hom.: 23060 Cov.: 33 AF XY: 0.534 AC XY: 39666 AN XY: 74304

African (AFR) AF: 0.700 AC: 29057 AN: 41484

American (AMR) AF: 0.382 AC: 5834 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1850 AN: 3472

East Asian (EAS) AF: 0.340 AC: 1761 AN: 5178

South Asian (SAS) AF: 0.443 AC: 2138 AN: 4824

European-Finnish (FIN) AF: 0.490 AC: 5163 AN: 10540

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34289 AN: 67966

Other (OTH) AF: 0.511 AC: 1080 AN: 2112

Alfa AF: 0.509 Hom.: 56315

Bravo AF: 0.537

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.39
PhyloP100		-0.0010
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: rs3010815; hg19: chr9-113434178; COSMIC: COSV51881056;