Submissions for variant NM_006279.5(ST3GAL3):c.362G>A (p.Arg121Gln)

gnomAD frequency: 0.00027  dbSNP: rs201287443

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000179462	SCV000231715	uncertain significance	not provided	2016-07-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000694658	SCV000823115	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 121 of the ST3GAL3 protein (p.Arg121Gln). This variant is present in population databases (rs201287443, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with ST3GAL3-related conditions. ClinVar contains an entry for this variant (Variation ID: 198193). 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 ST3GAL3 protein function. 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.
Fulgent Genetics, Fulgent Genetics	RCV000763923	SCV000894867	uncertain significance	Intellectual disability, autosomal recessive 12; Developmental and epileptic encephalopathy, 15	2018-10-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002453638	SCV002614164	uncertain significance	Inborn genetic diseases	2022-02-22	criteria provided, single submitter	clinical testing	The c.362G>A (p.R121Q) alteration is located in exon 6 (coding exon 5) of the ST3GAL3 gene. This alteration results from a G to A substitution at nucleotide position 362, causing the arginine (R) at amino acid position 121 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000763923	SCV003920508	uncertain significance	Intellectual disability, autosomal recessive 12; Developmental and epileptic encephalopathy, 15	2021-03-30	criteria provided, single submitter	clinical testing	ST3GAL3 NM_006279.4 exon 6 p.Arg121Gln (c.362G>A): This variant has not been reported in the literature but is present in 0.03% (27/68016) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/1-43894442-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:198193). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Breakthrough Genomics, Breakthrough Genomics	RCV000179462	SCV005186654	uncertain significance	not provided		criteria provided, single submitter	not provided
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000678851	SCV000805042	uncertain significance	Generalized myoclonic seizure	2017-03-31	no assertion criteria provided	clinical testing