ClinVar Miner

Submissions for variant NM_007255.3(B4GALT7):c.398A>G (p.Gln133Arg)

dbSNP: rs1370937766
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Genomic Medicine, Nationwide Children's Hospital RCV000779598 SCV000914236 uncertain significance Lethal skeletal dysplasia 2019-05-23 criteria provided, single submitter research This variant has been observed in 1 out of 120,473 gnomAD individuals (1 heterozygote, MAF=0.00000415), making it extremely rare. It is predicted to cause a missense change in the glycosyltransferase domain, and classified as damaging by a majority of in silico tools. In vitro enzyme assays confirmed a total lack of enzyme activity for this variant.
Invitae RCV001856177 SCV002168511 uncertain significance Ehlers-Danlos syndrome progeroid type 2021-10-14 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 133 of the B4GALT7 protein (p.Gln133Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with B4GALT7-related conditions (PMID: 31278392). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 632558). 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"). Experimental studies have shown that this missense change affects B4GALT7 function (PMID: 31278392). 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.
GeneDx RCV002462129 SCV002757014 pathogenic not provided 2022-11-16 criteria provided, single submitter clinical testing Published functional studies demonstrate a impaired protein localization and activity (Mihalic Mosher et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31278392, 34193099)
OMIM RCV003446432 SCV004171731 pathogenic Ehlers-Danlos syndrome, spondylodysplastic type, 1 2023-11-30 no assertion criteria provided literature only

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