ClinVar Miner

Submissions for variant NM_007255.3(B4GALT7):c.829G>T (p.Glu277Ter)

gnomAD frequency: 0.00001  dbSNP: rs1481659687
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Biology and Genetics, University of Brescia RCV001257134 SCV001371839 pathogenic Ehlers-Danlos syndrome progeroid type criteria provided, single submitter clinical testing this variant was annotated in dbSNP, and has extremely low frequencies in population genomic database. This variant was observed in two individuals in GnomAD (rs1481659687, 2/250434, no homozygotes, total MAF: C = 0.000007986). Both parents both parents (non-consaguineous) and her sister were heterozygotes. Sanger sequencing of RT-PCR showed in addition to mRNA resulting from the use of the canonical site, the presence of 2 further splice products: i) an allele derived from the activation of a cryptic splice acceptor site 3 bp downstream generating in frame deletion of the amino acid residue at position 277, and ii) mRNA with entire intron 5 retention causing the insertion of 10 amino acids followed by a stop codon. The mutation should therefore result in different amounts of truncated (p.Glu277* and p.Glu276_Glu277ins11*) and internally deleted polypeptides (p.Glu277del) leading to reduced galactosyltransferase activity.
Labcorp Genetics (formerly Invitae), Labcorp RCV001257134 SCV003439300 uncertain significance Ehlers-Danlos syndrome progeroid type 2022-03-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu277*) in the B4GALT7 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the B4GALT7 protein. This variant is present in population databases (no rsID available, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Ehlers-Danlos syndrome, spondylodysplastic type (PMID: 28882145). ClinVar contains an entry for this variant (Variation ID: 978463). Studies have shown that this premature translational stop signal is associated with altered splicing resulting in multiple RNA products (PMID: 28882145). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.