9-110695446-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005592.4(MUSK):​c.402G>C​(p.Glu134Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E134E) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.2e-7 ( 0 hom. )

Consequence

MUSK
NM_005592.4 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.227
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3177547).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MUSKNM_005592.4 linkc.402G>C p.Glu134Asp missense_variant Exon 4 of 15 ENST00000374448.9 NP_005583.1 O15146-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MUSKENST00000374448.9 linkc.402G>C p.Glu134Asp missense_variant Exon 4 of 15 5 NM_005592.4 ENSP00000363571.4 O15146-1
MUSKENST00000416899.7 linkc.402G>C p.Glu134Asp missense_variant Exon 4 of 14 5 ENSP00000393608.3 A0A087WSY1
MUSKENST00000189978.10 linkc.402G>C p.Glu134Asp missense_variant Exon 4 of 14 5 ENSP00000189978.6 O15146-2
MUSKENST00000374439.1 linkc.96G>C p.Glu32Asp missense_variant Exon 2 of 4 5 ENSP00000363562.2 F6XAJ2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.21e-7
AC:
1
AN:
1386614
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
686088
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:
9.40e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;.;.;.;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.18
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Uncertain
0.95
D;D;D;D;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.32
T;T;T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.6
M;.;M;.;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.1
N;N;N;.;.
REVEL
Benign
0.18
Sift
Benign
0.22
T;T;D;.;.
Sift4G
Benign
0.28
T;T;T;T;T
Polyphen
0.87
P;.;.;.;.
Vest4
0.40
MutPred
0.54
Loss of methylation at K131 (P = 0.09);Loss of methylation at K131 (P = 0.09);Loss of methylation at K131 (P = 0.09);Loss of methylation at K131 (P = 0.09);.;
MVP
0.30
MPC
0.54
ClinPred
0.91
D
GERP RS
-1.2
Varity_R
0.13
gMVP
0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-113457726; API