ClinVar Miner

Submissions for variant NM_080605.4(B3GALT6):c.895C>A (p.Leu299Met)

gnomAD frequency: 0.00011  dbSNP: rs374645024
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001576991 SCV001804293 uncertain significance not provided 2021-09-24 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV001866069 SCV002270244 uncertain significance Ehlers-Danlos syndrome, spondylodysplastic type, 2; Spondyloepimetaphyseal dysplasia with joint laxity 2022-09-12 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 299 of the B3GALT6 protein (p.Leu299Met). This variant is present in population databases (rs374645024, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with B3GALT6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1208606). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV002501932 SCV002814662 uncertain significance Al-Gazali syndrome; Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures; Ehlers-Danlos syndrome, spondylodysplastic type, 2 2022-03-17 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001576991 SCV005407949 uncertain significance not provided 2023-09-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005057522 SCV005726184 uncertain significance not specified 2024-11-19 criteria provided, single submitter clinical testing Variant summary: B3GALT6 c.895C>A (p.Leu299Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.3e-05 in 140478 control chromosomes, predominantly at a frequency of 0.00024 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in B3GALT6 causing Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures (9.3e-05 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.895C>A in individuals affected with Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1208606). Based on the evidence outlined above, the variant was classified as uncertain significance.

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