rs147974075

Variant names:

• chr9-110762231-AT-A
• rs147974075
• NM_005592.4:c.920+25delT

Your query was ambiguous. Multiple possible variants found:

• chr9-110762231-AT-A
• chr9-110762231-AT-ATT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005592.4(MUSK):​c.920+25delT variant causes a intron change involving the alteration of a non-conserved nucleotide. 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
• Publications: 1 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 -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 VariationId 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.

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+25delT		intron	N/A	NP_005583.1	O15146-1
	MUSK	NM_001166280.2		c.950+25delT		intron	N/A	NP_001159752.1	O15146-2
	MUSK	NM_001166281.2		c.920+25delT		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+25delT		intron	N/A	ENSP00000363571.4	O15146-1
	MUSK	ENST00000416899.7	TSL:5	c.920+25delT		intron	N/A	ENSP00000393608.3	A0A087WSY1
	MUSK	ENST00000189978.10	TSL:5	c.950+25delT		intron	N/A	ENSP00000189978.6	O15146-2

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

GnomAD2 exomes AF: 0.387 AC: 64621 AN: 166922 AF XY: 0.395

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 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

African (AFR) AF: 0.314 AC: 8846 AN: 28208

American (AMR) AF: 0.242 AC: 7126 AN: 29400

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 10800 AN: 20582

East Asian (EAS) AF: 0.124 AC: 4376 AN: 35174

South Asian (SAS) AF: 0.303 AC: 17135 AN: 56462

European-Finnish (FIN) AF: 0.461 AC: 15403 AN: 33418

Middle Eastern (MID) AF: 0.492 AC: 2510 AN: 5104

European-Non Finnish (NFE) AF: 0.473 AC: 478709 AN: 1012874

Other (OTH) AF: 0.427 AC: 22325 AN: 52332

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

African (AFR) AF: 0.333 AC: 13805 AN: 41410

American (AMR) AF: 0.345 AC: 5268 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1835 AN: 3460

East Asian (EAS) AF: 0.104 AC: 538 AN: 5172

South Asian (SAS) AF: 0.311 AC: 1496 AN: 4806

European-Finnish (FIN) AF: 0.468 AC: 4932 AN: 10546

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32864 AN: 67938

Other (OTH) AF: 0.438 AC: 925 AN: 2112

Alfa AF: 0.441 Hom.: 2867

Bravo AF: 0.396

Asia WGS AF: 0.203 AC: 709 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital myasthenic syndrome 9 (1)
-	-	1	Fetal akinesia deformation sequence 1 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs147974075; hg19: chr9-113524511;