NM_000080.4(CHRNE):c.1439A>G (p.Asn480Ser) AND Congenital myasthenic syndrome 4A

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 28, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001921135.3

Allele description [Variation Report for NM_000080.4(CHRNE):c.1439A>G (p.Asn480Ser)]

NM_000080.4(CHRNE):c.1439A>G (p.Asn480Ser)

Gene:

CHRNE:cholinergic receptor nicotinic epsilon subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_000080.4(CHRNE):c.1439A>G (p.Asn480Ser)

HGVS:

NC_000017.11:g.4898779T>C
NG_008029.2:g.9297A>G
NG_028005.1:g.70440T>C
NM_000080.4:c.1439A>GMANE SELECT
NP_000071.1:p.Asn480Ser
LRG_1254t1:c.1439A>G
LRG_1254:g.9297A>G
LRG_1254p1:p.Asn480Ser
NC_000017.10:g.4802074T>C

Protein change:

N480S

Links:

dbSNP: rs760738362

NCBI 1000 Genomes Browser:

rs760738362

Molecular consequence:

NM_000080.4:c.1439A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital myasthenic syndrome 4A
Synonyms:: CONGENITAL MYASTHENIC SYNDROME TYPE Ia1; Myasthenic syndrome, congenital, 4a, slow-channel; MYASTHENIC SYNDROME, CONGENITAL, 4A, SLOW-CHANNEL, AUTOSOMAL RECESSIVE
Identifiers:: MONDO: MONDO:0011600; MedGen: C4225413; Orphanet: 590; OMIM: 605809

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002197308	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 28, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002197308

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 28, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002197308.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 480 of the CHRNE protein (p.Asn480Ser). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CHRNE-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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