Submissions for variant NM_012200.4(B3GAT3):c.1A>T (p.Met1Leu)

gnomAD frequency: 0.00002  dbSNP: rs139759238

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002568864	SCV003460187	likely pathogenic	Larsen-like syndrome, B3GAT3 type	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change affects the initiator methionine of the B3GAT3 mRNA. The next in-frame methionine is located at codon 207. This variant is present in population databases (rs139759238, gnomAD 0.005%). Disruption of the initiator codon has been observed in individual(s) with B3GAT3-related conditions (PMID: 27871226). ClinVar contains an entry for this variant (Variation ID: 1174609). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of the initiator codon affects B3GAT3 function (PMID: 27871226). This variant disrupts a region of the B3GAT3 protein in which other variant(s) (p.Arg161Trp) have been observed in individuals with B3GAT3-related conditions (PMID: 31438591). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx	RCV001528207	SCV003925861	pathogenic	not provided	2022-11-21	criteria provided, single submitter	clinical testing	Initiation codon variant in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528207	SCV001739528	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001528207	SCV001809507	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528207	SCV001967998	likely pathogenic	not provided		no assertion criteria provided	clinical testing