Submissions for variant NM_021912.5(GABRB3):c.31C>T (p.Pro11Ser)

gnomAD frequency: 0.00354  dbSNP: rs25409

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000203153	SCV000258180	likely benign	not specified	2015-05-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001701568	SCV000513096	benign	not provided	2019-04-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26645412, 22206818, 20550555, 19935738, 18514161, 20308251, 27884173, 31435640)
Athena Diagnostics	RCV000203153	SCV000613366	benign	not specified	2016-12-02	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000017575	SCV000782445	uncertain significance	Epilepsy, childhood absence, susceptibility to, 5	2016-05-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002313713	SCV000849397	benign	Inborn genetic diseases	2016-09-16	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics	RCV000989276	SCV001139532	benign	Epilepsy, childhood absence, susceptibility to, 1	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001511952	SCV001719277	benign	Epilepsy, childhood absence, susceptibility to, 1; Epilepsy, childhood absence, susceptibility to, 5	2023-12-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001701568	SCV002497748	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	GABRB3: PP2, BP4, BS1, BS2
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224101	SCV003919997	likely benign	Epilepsy, childhood absence, susceptibility to, 5; Developmental and epileptic encephalopathy, 43	2022-10-24	criteria provided, single submitter	clinical testing	GABRB3 NM_021912.5 exon 1 p.Pro11Ser (c.31C>T): This variant has been reported in the literature in at least 2 individuals with absence epilepsy and numerous individuals with autism (Tanaka 2008 PMID:185141461, Delahanty 2011 PMID:19935738). However, this variant is present in 0.5% (370/67998) of European alleles including 2 homozygotes, as well as 1 homozygote in the South Asian population in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/15-26773694-G-A?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as Likely Benign or Benign (Variation ID:16191). Evolutionary conservation for this variant is limited or unavailable; computational predictive tools suggest that this variant may not impact the protein. In vitro functional studies suggests that this variant may impact the protein, however, this data may not represent in vivo biological function (Tanaka 2008 PMID:185141461, Shi 2019 PMID:31435640). In summary, data on this variant, particularly the minor allele frequency and presence of homozygotes in ostensibly unaffected individuals suggests that this variant does not cause disease, but requires further evidence. Therefore this variant is classified as Likely Benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001701568	SCV004564680	benign	not provided	2023-10-13	criteria provided, single submitter	clinical testing
OMIM	RCV000017575	SCV000037847	risk factor	Epilepsy, childhood absence, susceptibility to, 5	2008-06-01	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001701568	SCV001932694	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001701568	SCV001966306	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003934836	SCV004752053	benign	GABRB3-related disorder	2020-06-05	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).