9-110798971-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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)
• fetal akinesia deformation sequence 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005592.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUSK	NM_005592.4	MANE Select	c.1928-1335T>G		intron	N/A	NP_005583.1	O15146-1
	MUSK	NM_001166280.2		c.1670-1335T>G		intron	N/A	NP_001159752.1	O15146-2
	MUSK	NM_001166281.2		c.1640-1335T>G		intron	N/A	NP_001159753.1	O15146-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUSK	ENST00000374448.9	TSL:5 MANE Select	c.1928-1335T>G		intron	N/A	ENSP00000363571.4	O15146-1
	MUSK	ENST00000416899.7	TSL:5	c.1904-1335T>G		intron	N/A	ENSP00000393608.3	A0A087WSY1
	MUSK	ENST00000189978.10	TSL:5	c.1670-1335T>G		intron	N/A	ENSP00000189978.6	O15146-2

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

African (AFR) AF: 0.0217 AC: 903 AN: 41542

American (AMR) AF: 0.0572 AC: 875 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3472

East Asian (EAS) AF: 0.170 AC: 876 AN: 5156

South Asian (SAS) AF: 0.178 AC: 858 AN: 4818

European-Finnish (FIN) AF: 0.149 AC: 1569 AN: 10554

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9046 AN: 67962

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.113 Hom.: 2027

Bravo AF: 0.0848

Asia WGS AF: 0.148 AC: 510 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.80
PhyloP100		0.010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3780529; hg19: chr9-113561251;