Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001343983 | SCV001538010 | uncertain significance | not provided | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 535 of the GALNT12 protein (p.Glu535Asp). This variant also falls at the last nucleotide of exon 9, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GALNT12-related conditions. ClinVar contains an entry for this variant (Variation ID: 1040360). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Ambry Genetics | RCV004036413 | SCV002709581 | uncertain significance | not specified | 2023-04-24 | criteria provided, single submitter | clinical testing | The p.E535D variant (also known as c.1605G>T), located in coding exon 9 of the GALNT12 gene, results from a G to T substitution at nucleotide position 1605. The amino acid change results in glutamic acid to aspartic acid at codon 535, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 9 and may have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV004570827 | SCV005058797 | uncertain significance | Colorectal cancer, susceptibility to, 1 | 2024-03-11 | criteria provided, single submitter | clinical testing |