rs3010815

chr9-110671898-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.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

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=-0.89).
• 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/exons	MANE	UniProt
MUSK	NM_005592.4	c.79+2915C>T		intron_variant		ENST00000374448.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUSK	ENST00000374448.9	c.79+2915C>T		intron_variant		5	NM_005592.4	P4
MUSK	ENST00000189978.10	c.79+2915C>T		intron_variant		5
MUSK	ENST00000416899.7	c.79+2915C>T		intron_variant		5		A1

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

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.511

Alfa AF: 0.507 Hom.: 39259

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

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: rs3010815; hg19: chr9-113434178; COSMIC: COSV51881056;