NM_001127644.2(GABRA1):c.312T>G (p.Phe104Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 8, 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:: RCV001976150.6

Allele description [Variation Report for NM_001127644.2(GABRA1):c.312T>G (p.Phe104Leu)]

NM_001127644.2(GABRA1):c.312T>G (p.Phe104Leu)

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.312T>G (p.Phe104Leu)

HGVS:

NC_000005.10:g.161873173T>G
NG_011548.1:g.30983T>G
NM_000806.5:c.312T>G
NM_001127643.2:c.312T>G
NM_001127644.2:c.312T>GMANE SELECT
NM_001127645.2:c.312T>G
NM_001127648.2:c.312T>G
NP_000797.2:p.Phe104Leu
NP_001121115.1:p.Phe104Leu
NP_001121116.1:p.Phe104Leu
NP_001121117.1:p.Phe104Leu
NP_001121120.1:p.Phe104Leu
NC_000005.9:g.161300179T>G

Protein change:

F104L

Links:

dbSNP: rs2113381036

NCBI 1000 Genomes Browser:

rs2113381036

Molecular consequence:

NM_000806.5:c.312T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127643.2:c.312T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127644.2:c.312T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127645.2:c.312T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127648.2:c.312T>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002260679	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 8, 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

SCV002260679

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 8, 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, SCV002260679.3

#	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 phenylalanine with leucine at codon 104 of the GABRA1 protein (p.Phe104Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. 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. 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"). This variant has not been reported in the literature in individuals with GABRA1-related conditions. This variant is not present in population databases (ExAC no frequency).

#	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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