rs1555546304
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000080.4(CHRNE):c.1117T>G(p.Ser373Ala) variant causes a missense 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S373S) has been classified as Benign.
Frequency
Genomes: not found (cov: 32)
Consequence
CHRNE
NM_000080.4 missense
NM_000080.4 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 0.608
Genes affected
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNE | NM_000080.4 | c.1117T>G | p.Ser373Ala | missense_variant | 10/12 | ENST00000649488.2 | |
CHRNE | XM_017024115.2 | c.1081T>G | p.Ser361Ala | missense_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNE | ENST00000649488.2 | c.1117T>G | p.Ser373Ala | missense_variant | 10/12 | NM_000080.4 | P1 | ||
CHRNE | ENST00000649830.1 | c.184T>G | p.Ser62Ala | missense_variant | 10/11 | ||||
CHRNE | ENST00000572438.1 | n.803T>G | non_coding_transcript_exon_variant | 5/7 | 5 | ||||
CHRNE | ENST00000652550.1 | n.847T>G | non_coding_transcript_exon_variant | 2/4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital myasthenic syndrome 4A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CHRNE protein function. ClinVar contains an entry for this variant (Variation ID: 534257). This variant has not been reported in the literature in individuals affected with CHRNE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 373 of the CHRNE protein (p.Ser373Ala). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
.;T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;.
Sift4G
Uncertain
D;.;.
Polyphen
D;D;.
Vest4
MutPred
Loss of phosphorylation at S373 (P = 0.0013);Loss of phosphorylation at S373 (P = 0.0013);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at