chr17-4899465-T-TACGTGGCGCAGCCGCGGGG
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_000080.4(CHRNE):c.1032+2_1032+3insCCCCGCGGCTGCGCCACGT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
CHRNE
NM_000080.4 splice_region, intron
NM_000080.4 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.14
Genes affected
C17orf107 (HGNC:37238): (chromosome 17 open reading frame 107)
CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-4899465-T-TACGTGGCGCAGCCGCGGGG is Pathogenic according to our data. Variant chr17-4899465-T-TACGTGGCGCAGCCGCGGGG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2692228.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNE | NM_000080.4 | c.1032+2_1032+3insCCCCGCGGCTGCGCCACGT | splice_region_variant, intron_variant | ENST00000649488.2 | |||
CHRNE | XM_017024115.2 | c.996+2_996+3insCCCCGCGGCTGCGCCACGT | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNE | ENST00000649488.2 | c.1032+2_1032+3insCCCCGCGGCTGCGCCACGT | splice_region_variant, intron_variant | NM_000080.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Congenital myasthenic syndrome 4B Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Breakthrough Genomics, Breakthrough Genomics | - | This variant seems to be a novel variant, as it has not been previously reported in population or public databases or in the literature. However, splice variants, lying downstream of the variant, have been reported as pathogenic/likely pathogenic in the ClinVar database in the context of slow-channel congenital myasthenic syndrome 4a. Loss-of-function variants in the CHRNE are known to be pathogenic [PMID: 22678886] - |
Congenital myasthenic syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Breakthrough Genomics, Breakthrough Genomics | Nov 26, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.