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NM_001127644.2(GABRA1):c.385C>T (p.His129Tyr) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 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:
RCV002047820.5

Allele description

NM_001127644.2(GABRA1):c.385C>T (p.His129Tyr)

Gene:
GABRA1:gamma-aminobutyric acid type A receptor subunit alpha1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q34
Genomic location:
Preferred name:
NM_001127644.2(GABRA1):c.385C>T (p.His129Tyr)
HGVS:
  • NC_000005.10:g.161873246C>T
  • NG_011548.1:g.31056C>T
  • NM_000806.5:c.385C>T
  • NM_001127643.2:c.385C>T
  • NM_001127644.2:c.385C>TMANE SELECT
  • NM_001127645.2:c.385C>T
  • NM_001127648.2:c.385C>T
  • NP_000797.2:p.His129Tyr
  • NP_001121115.1:p.His129Tyr
  • NP_001121116.1:p.His129Tyr
  • NP_001121117.1:p.His129Tyr
  • NP_001121120.1:p.His129Tyr
  • NC_000005.9:g.161300252C>T
Protein change:
H129Y
Links:
dbSNP: rs146134200
NCBI 1000 Genomes Browser:
rs146134200
Molecular consequence:
  • NM_000806.5:c.385C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127643.2:c.385C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127644.2:c.385C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127645.2:c.385C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127648.2:c.385C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Idiopathic generalized epilepsy
Synonyms:
EIG; Generalised epilepsy
Identifiers:
MONDO: MONDO:0005579; MedGen: C0270850; OMIM: 600669; OMIM: PS600669
Name:
Epilepsy, idiopathic generalized, susceptibility to, 13
Synonyms:
EPILEPSY, JUVENILE MYOCLONIC, SUSCEPTIBILITY TO, 5; Epilepsy, juvenile myoclonic 5
Identifiers:
MONDO: MONDO:0012627; MedGen: C4013473; Orphanet: 307; Orphanet: 64280; OMIM: 611136
Name:
Epilepsy, childhood absence 4 (ECA4)
Synonyms:
EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 4
Identifiers:
MedGen: C1970160; Orphanet: 307

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002296525Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 25, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Deleterious Rare Variants Reveal Risk for Loss of GABAA Receptor Function in Patients with Genetic Epilepsy and in the General Population.

Hernandez CC, Klassen TL, Jackson LG, Gurba K, Hu N, Noebels JL, Macdonald RL.

PLoS One. 2016;11(9):e0162883. doi: 10.1371/journal.pone.0162883. Erratum in: PLoS One. 2016 Nov 21;11(11):e0167264. doi: 10.1371/journal.pone.0167264.

PubMed [citation]
PMID:
27622563
PMCID:
PMC5021343

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 Invitae, SCV002296525.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

ClinVar contains an entry for this variant (Variation ID: 1504517). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on GABRA1 function (PMID: 27622563). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GABRA1 protein function. This variant has not been reported in the literature in individuals affected with GABRA1-related conditions. This variant is present in population databases (rs146134200, gnomAD 0.01%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 129 of the GABRA1 protein (p.His129Tyr).

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

Last Updated: Mar 5, 2024