rs147974075

chr9-110762231-AT-Achr9-110762231-AT-ATT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005592.4(MUSK):c.920+25del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 1,425,480 control chromosomes in the GnomAD database, including 145,073 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13552 hom., cov: 0)
  • Exomes 𝑓: 0.45 (131521 hom.)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.00

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]

LOC107987115 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 9-110762231-AT-A is Benign according to our data. Variant chr9-110762231-AT-A is described in ClinVar as [Benign]. Clinvar id is 259813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUSK	NM_005592.4	c.920+25del		intron_variant		ENST00000374448.9
LOC107987115	XR_001746892.2	n.2863del		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUSK	ENST00000374448.9	c.920+25del		intron_variant		5	NM_005592.4	P4
MUSK	ENST00000189978.10	c.950+25del		intron_variant		5
MUSK	ENST00000416899.7	c.920+25del		intron_variant		5		A1
MUSK	ENST00000634612.1	n.342+25del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62325 AN: 151808 Hom.: 13548 Cov.: 0

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.442

GnomAD3 exomes AF: 0.387 AC: 64621 AN: 166922 Hom.: 13940 AF XY: 0.395 AC XY: 36467 AN XY: 92208

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.511

Gnomad EAS exome AF: 0.0961

Gnomad SAS exome AF: 0.306

Gnomad FIN exome AF: 0.457

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.445 AC: 567230 AN: 1273554 Hom.: 131521 Cov.: 0 AF XY: 0.443 AC XY: 277163 AN XY: 626286

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.525

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.410 AC: 62354 AN: 151926 Hom.: 13552 Cov.: 0 AF XY: 0.407 AC XY: 30203 AN XY: 74254

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.438

Alfa AF: 0.441 Hom.: 2867

Bravo AF: 0.396

Asia WGS AF: 0.203 AC: 709 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Fetal akinesia deformation sequence 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

Congenital myasthenic syndrome 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs147974075; hg19: chr9-113524511;