NM_005592.4:c.79+14A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005592.4(MUSK):​c.79+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MUSK
NM_005592.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.385

Publications

0 publications found
Variant links:
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), PanelApp Australia
  • fetal akinesia deformation sequence 1
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
  • postsynaptic congenital myasthenic syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 9-110668997-A-G is Benign according to our data. Variant chr9-110668997-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2948534.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MUSKNM_005592.4 linkc.79+14A>G intron_variant Intron 1 of 14 ENST00000374448.9 NP_005583.1 O15146-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MUSKENST00000374448.9 linkc.79+14A>G intron_variant Intron 1 of 14 5 NM_005592.4 ENSP00000363571.4 O15146-1
MUSKENST00000416899.7 linkc.79+14A>G intron_variant Intron 1 of 13 5 ENSP00000393608.3 A0A087WSY1
MUSKENST00000189978.10 linkc.79+14A>G intron_variant Intron 1 of 13 5 ENSP00000189978.6 O15146-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000401
AC:
1
AN:
249108
AF XY:
0.00000740
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1451596
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
722898
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33230
American (AMR)
AF:
0.00
AC:
0
AN:
44686
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26076
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39654
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86054
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53394
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1102726
Other (OTH)
AF:
0.00
AC:
0
AN:
60030
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Fetal akinesia deformation sequence 1;C4225368:Congenital myasthenic syndrome 9 Benign:1
Sep 30, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely 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
-0.87
CADD
Benign
2.8
DANN
Benign
0.53
PhyloP100
0.39
PromoterAI
-0.080
Neutral

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

Other links and lift over

dbSNP: rs1345348874; hg19: chr9-113431277; API