rs41279051

Variant names:

• chr9-110697375-C-T
• rs41279051
• NM_005592.4:c.537C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-110697375-C-T
• chr9-110697375-C-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005592.4(MUSK):​c.537C>T​(p.Asn179Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,610,998 control chromosomes in the GnomAD database, including 25,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1786 hom., cov: 31)
  • Exomes 𝑓: 0.18 (23880 hom.)
• Consequence: MUSK NM_005592.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0990
• Publications: 13 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 9-110697375-C-T is Benign according to our data. Variant chr9-110697375-C-T is described in ClinVar as Benign. ClinVar VariationId is 129637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.099 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 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.537C>T	p.Asn179Asn	synonymous	Exon 5 of 15	NP_005583.1	O15146-1
	MUSK	NM_001166280.2		c.537C>T	p.Asn179Asn	synonymous	Exon 5 of 14	NP_001159752.1	O15146-2
	MUSK	NM_001166281.2		c.537C>T	p.Asn179Asn	synonymous	Exon 5 of 13	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.537C>T	p.Asn179Asn	synonymous	Exon 5 of 15	ENSP00000363571.4	O15146-1
	MUSK	ENST00000416899.7	TSL:5	c.537C>T	p.Asn179Asn	synonymous	Exon 5 of 14	ENSP00000393608.3	A0A087WSY1
	MUSK	ENST00000189978.10	TSL:5	c.537C>T	p.Asn179Asn	synonymous	Exon 5 of 14	ENSP00000189978.6	O15146-2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20532 AN: 151848 Hom.: 1780 Cov.: 31

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.109

GnomAD2 exomes AF: 0.161 AC: 39982 AN: 248244 AF XY: 0.167

Gnomad AFR exome AF: 0.0262

Gnomad AMR exome AF: 0.0661

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.194

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.177 AC: 258273 AN: 1459032 Hom.: 23880 Cov.: 31 AF XY: 0.178 AC XY: 129126 AN XY: 725780

African (AFR) AF: 0.0259 AC: 867 AN: 33448

American (AMR) AF: 0.0695 AC: 3098 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4821 AN: 26070

East Asian (EAS) AF: 0.184 AC: 7292 AN: 39600

South Asian (SAS) AF: 0.180 AC: 15449 AN: 85712

European-Finnish (FIN) AF: 0.246 AC: 13130 AN: 53290

Middle Eastern (MID) AF: 0.141 AC: 813 AN: 5764

European-Non Finnish (NFE) AF: 0.183 AC: 202898 AN: 1110272

Other (OTH) AF: 0.164 AC: 9905 AN: 60274

GnomAD4 genome AF: 0.135 AC: 20542 AN: 151966 Hom.: 1786 Cov.: 31 AF XY: 0.139 AC XY: 10297 AN XY: 74274

African (AFR) AF: 0.0301 AC: 1247 AN: 41480

American (AMR) AF: 0.0891 AC: 1361 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 650 AN: 3468

East Asian (EAS) AF: 0.197 AC: 1018 AN: 5162

South Asian (SAS) AF: 0.175 AC: 841 AN: 4814

European-Finnish (FIN) AF: 0.257 AC: 2704 AN: 10510

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12273 AN: 67952

Other (OTH) AF: 0.113 AC: 239 AN: 2108

Alfa AF: 0.154 Hom.: 1678

Bravo AF: 0.117

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Congenital myasthenic syndrome 9 (1)
-	-	1	Fetal akinesia deformation sequence 1;C4225368:Congenital myasthenic syndrome 9 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.099
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41279051; hg19: chr9-113459655; COSMIC: COSV51878479;