9-110668943-T-TA
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_005592.4(MUSK):c.40dup(p.Thr14AsnfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
MUSK
NM_005592.4 frameshift
NM_005592.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.96
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 Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 55 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 9-110668943-T-TA is Pathogenic according to our data. Variant chr9-110668943-T-TA is described in ClinVar as [Pathogenic]. Clinvar id is 190466.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUSK | NM_005592.4 | c.40dup | p.Thr14AsnfsTer9 | frameshift_variant | 1/15 | ENST00000374448.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUSK | ENST00000374448.9 | c.40dup | p.Thr14AsnfsTer9 | frameshift_variant | 1/15 | 5 | NM_005592.4 | P4 | |
MUSK | ENST00000189978.10 | c.40dup | p.Thr14AsnfsTer9 | frameshift_variant | 1/14 | 5 | |||
MUSK | ENST00000416899.7 | c.40dup | p.Thr14AsnfsTer9 | frameshift_variant | 1/14 | 5 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249192Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135184
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461520Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727046
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Fetal akinesia deformation sequence 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2015 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at