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NM_000744.7(CHRNA4):c.505C>T (p.Pro169Ser) AND Autosomal dominant nocturnal frontal lobe epilepsy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 27, 2022
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:
RCV003835272.2

Allele description [Variation Report for NM_000744.7(CHRNA4):c.505C>T (p.Pro169Ser)]

NM_000744.7(CHRNA4):c.505C>T (p.Pro169Ser)

Gene:
CHRNA4:cholinergic receptor nicotinic alpha 4 subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.33
Genomic location:
Preferred name:
NM_000744.7(CHRNA4):c.505C>T (p.Pro169Ser)
HGVS:
  • NC_000020.11:g.63350906G>A
  • NG_011931.1:g.15438C>T
  • NM_000744.7:c.505C>TMANE SELECT
  • NM_001256573.2:c.-24C>T
  • NP_000735.1:p.Pro169Ser
  • NC_000020.10:g.61982258G>A
  • NR_046317.2:n.714C>T
Protein change:
P169S
Molecular consequence:
  • NM_001256573.2:c.-24C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000744.7:c.505C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_046317.2:n.714C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)
Identifiers:
MONDO: MONDO:0020300; MedGen: C3696898

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004630721Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 27, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV004630721.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 169 of the CHRNA4 protein (p.Pro169Ser). This variant is not present in population databases (gnomAD no frequency). 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 expected to disrupt CHRNA4 protein function. This missense change has been observed in at least one individual who was not affected with CHRNA4-related conditions (Invitae). This variant has not been reported in the literature in individuals affected with CHRNA4-related conditions.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024