rs144807641

Variant names:

• chr9-110687288-G-A
• rs144807641
• NM_005592.4:c.358+20G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-110687288-G-A
• chr9-110687288-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005592.4(MUSK):​c.358+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,612,348 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (3 hom.)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.44

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 9-110687288-G-A is Benign according to our data. Variant chr9-110687288-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000855 (130/152084) while in subpopulation NFE AF= 0.0014 (95/67958). AF 95% confidence interval is 0.00117. There are 0 homozygotes in gnomad4. There are 55 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUSK	NM_005592.4	c.358+20G>A		intron_variant	Intron 3 of 14	ENST00000374448.9	NP_005583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUSK	ENST00000374448.9	c.358+20G>A		intron_variant	Intron 3 of 14	5	NM_005592.4	ENSP00000363571.4
MUSK	ENST00000416899.7	c.358+20G>A		intron_variant	Intron 3 of 13	5		ENSP00000393608.3
MUSK	ENST00000189978.10	c.358+20G>A		intron_variant	Intron 3 of 13	5		ENSP00000189978.6
MUSK	ENST00000374439.1	c.52+20G>A		intron_variant	Intron 1 of 3	5		ENSP00000363562.2

Frequencies

GnomAD3 genomes AF: 0.000855 AC: 130 AN: 151966 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00126 AC: 312 AN: 248120 Hom.: 1 AF XY: 0.00115 AC XY: 155 AN XY: 134540

Gnomad AFR exome AF: 0.000452

Gnomad AMR exome AF: 0.000350

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00233

Gnomad NFE exome AF: 0.00212

Gnomad OTH exome AF: 0.000829

GnomAD4 exome AF: 0.00120 AC: 1749 AN: 1460264 Hom.: 3 Cov.: 31 AF XY: 0.00115 AC XY: 832 AN XY: 726400

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000494

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00236

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.000780

GnomAD4 genome AF: 0.000855 AC: 130 AN: 152084 Hom.: 0 Cov.: 31 AF XY: 0.000739 AC XY: 55 AN XY: 74376

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000569 Hom.: 0

Bravo AF: 0.000771

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jul 13, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fetal akinesia deformation sequence 1;C4225368:Congenital myasthenic syndrome 9 Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0070
DANN	Benign	0.29

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: rs144807641; hg19: chr9-113449568; COSMIC: COSV99503664;