9-110798971-T-G

Variant names:

• chr9-110798971-T-G
• rs3780529
• NM_005592.4:c.1928-1335T>G

Variant summary

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

The NM_005592.4(MUSK):​c.1928-1335T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 152,112 control chromosomes in the GnomAD database, including 935 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 0.097 (935 hom., cov: 32)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUSK	NM_005592.4	c.1928-1335T>G		intron_variant	Intron 14 of 14	ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.1928-1335T>G		intron_variant	Intron 14 of 14	5	NM_005592.4	ENSP00000363571.4
MUSK	ENST00000416899.7	c.1904-1335T>G		intron_variant	Intron 13 of 13	5		ENSP00000393608.3
MUSK	ENST00000189978.10	c.1670-1335T>G		intron_variant	Intron 13 of 13	5		ENSP00000189978.6

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14819 AN: 151994 Hom.: 935 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0974 AC: 14818 AN: 152112 Hom.: 935 Cov.: 32 AF XY: 0.0988 AC XY: 7348 AN XY: 74348

Gnomad4 AFR AF: 0.0217

Gnomad4 AMR AF: 0.0572

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.118 Hom.: 1696

Bravo AF: 0.0848

Asia WGS AF: 0.148 AC: 510 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs3780529; hg19: chr9-113561251;