rs10817091

Variant names:

• chr9-110764946-G-A
• rs10817091
• NM_005592.4:c.920+2738G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-110764946-G-A
• chr9-110764946-G-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.920+2738G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,728 control chromosomes in the GnomAD database, including 12,095 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 0.38 (12095 hom., cov: 31)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 4 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

LOC107987115 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.463 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.920+2738G>A		intron	N/A	NP_005583.1	O15146-1
	MUSK	NM_001166280.2		c.950+2738G>A		intron	N/A	NP_001159752.1	O15146-2
	MUSK	NM_001166281.2		c.920+2738G>A		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.920+2738G>A		intron	N/A	ENSP00000363571.4	O15146-1
	MUSK	ENST00000416899.7	TSL:5	c.920+2738G>A		intron	N/A	ENSP00000393608.3	A0A087WSY1
	MUSK	ENST00000189978.10	TSL:5	c.950+2738G>A		intron	N/A	ENSP00000189978.6	O15146-2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58110 AN: 151610 Hom.: 12093 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.0895

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.383 AC: 58121 AN: 151728 Hom.: 12095 Cov.: 31 AF XY: 0.380 AC XY: 28211 AN XY: 74144

African (AFR) AF: 0.276 AC: 11415 AN: 41356

American (AMR) AF: 0.322 AC: 4904 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1811 AN: 3468

East Asian (EAS) AF: 0.0894 AC: 462 AN: 5170

South Asian (SAS) AF: 0.281 AC: 1348 AN: 4804

European-Finnish (FIN) AF: 0.465 AC: 4869 AN: 10464

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31757 AN: 67904

Other (OTH) AF: 0.419 AC: 883 AN: 2108

Alfa AF: 0.438 Hom.: 64434

Bravo AF: 0.368

Asia WGS AF: 0.184 AC: 640 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.045
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: rs10817091; hg19: chr9-113527226;