NM_000814.6(GABRB3):c.1127A>G (p.Asn376Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 25, 2023
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:: RCV001228195.14

Allele description [Variation Report for NM_000814.6(GABRB3):c.1127A>G (p.Asn376Ser)]

NM_000814.6(GABRB3):c.1127A>G (p.Asn376Ser)

Gene:

GABRB3:gamma-aminobutyric acid type A receptor subunit beta3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q12

Genomic location:

Preferred name:

NM_000814.6(GABRB3):c.1127A>G (p.Asn376Ser)

HGVS:

NC_000015.10:g.26548088T>C
NG_012836.1:g.230693A>G
NM_000814.6:c.1127A>GMANE SELECT
NM_001191320.2:c.872A>G
NM_001191321.3:c.914A>G
NM_001278631.2:c.872A>G
NM_021912.5:c.1127A>G
NP_000805.1:p.Asn376Ser
NP_001178249.1:p.Asn291Ser
NP_001178250.1:p.Asn305Ser
NP_001265560.1:p.Asn291Ser
NP_068712.1:p.Asn376Ser
NC_000015.9:g.26793235T>C
NM_000814.5:c.1127A>G

Protein change:

N291S

Links:

dbSNP: rs756866953

NCBI 1000 Genomes Browser:

rs756866953

Molecular consequence:

NM_000814.6:c.1127A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001191320.2:c.872A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001191321.3:c.914A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001278631.2:c.872A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_021912.5:c.1127A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Epilepsy, childhood absence, susceptibility to, 1
Synonyms:: Epilepsy, childhood absence 1
Identifiers:: MONDO: MONDO:0020759; MedGen: C1838604; Orphanet: 64280; OMIM: 600131

Name:: Epilepsy, childhood absence, susceptibility to, 5
Synonyms:: Epilepsy, childhood absence 5
Identifiers:: MONDO: MONDO:0012843; MedGen: C2677087; Orphanet: 64280; OMIM: 612269

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001400581	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 25, 2023)	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

SCV001400581

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 25, 2023)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001400581.5

#	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 376 of the GABRB3 protein (p.Asn376Ser). This variant is present in population databases (rs756866953, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with GABRB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 588438). 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 GABRB3 protein function with a negative predictive value of 95%. 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: Apr 15, 2024

ClinVar

Relating variation to medicine