9-110668924-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005592.4(MUSK):ā€‹c.20T>Cā€‹(p.Ile7Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,454 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000082 ( 0 hom. )

Consequence

MUSK
NM_005592.4 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MUSKNM_005592.4 linkuse as main transcriptc.20T>C p.Ile7Thr missense_variant 1/15 ENST00000374448.9 NP_005583.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MUSKENST00000374448.9 linkuse as main transcriptc.20T>C p.Ile7Thr missense_variant 1/155 NM_005592.4 ENSP00000363571 P4O15146-1
MUSKENST00000416899.7 linkuse as main transcriptc.20T>C p.Ile7Thr missense_variant 1/145 ENSP00000393608 A1
MUSKENST00000189978.10 linkuse as main transcriptc.20T>C p.Ile7Thr missense_variant 1/145 ENSP00000189978 O15146-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461454
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727010
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingRevvity Omics, RevvityNov 27, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.67
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T;.;.;.
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.85
T;T;T;T
M_CAP
Benign
0.047
D
MetaRNN
Uncertain
0.45
T;T;T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
0.69
N;.;N;.
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.66
N;N;N;.
REVEL
Uncertain
0.36
Sift
Benign
0.13
T;T;T;.
Sift4G
Benign
0.17
T;T;T;T
Polyphen
0.70
P;.;.;.
Vest4
0.58
MutPred
0.44
Loss of stability (P = 7e-04);Loss of stability (P = 7e-04);Loss of stability (P = 7e-04);Loss of stability (P = 7e-04);
MVP
0.78
MPC
0.44
ClinPred
0.64
D
GERP RS
5.2
Varity_R
0.099
gMVP
0.58

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2075922654; hg19: chr9-113431204; API