ClinVar Miner

Submissions for variant NM_024105.4(ALG12):c.449A>G (p.Asn150Ser)

gnomAD frequency: 0.00001  dbSNP: rs2060570009
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001933043 SCV002194418 uncertain significance ALG12-congenital disorder of glycosylation 2024-02-16 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 150 of the ALG12 protein (p.Asn150Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALG12-related conditions. ClinVar contains an entry for this variant (Variation ID: 1415356). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ALG12 protein function with a positive predictive value of 80%. 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 RCV002557698 SCV003667502 uncertain significance Inborn genetic diseases 2020-07-23 criteria provided, single submitter clinical testing The alteration results in an amino acid change:_x000D_ _x000D_ The c.449A>G (p.N150S) alteration is located in exon 4 (coding exon 3) of the ALG12 gene. This alteration results from an A to G substitution at nucleotide position 449, causing the asparagine (N) at amino acid position 150 to be replaced by a serine (S). The alteration is not observed in population databases:_x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the ALG12 c.449A>G alteration was not observed, with coverage at this position. The altered amino acid is conserved throughout evolution:_x000D_ _x000D_ The p.N150 amino acid is conserved in available vertebrate species. The alteration is predicted tolerated by in silico modeling:_x000D_ _x000D_ The p.N150S alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV005235606 SCV005882158 likely pathogenic not provided 2024-09-09 criteria provided, single submitter clinical testing 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: 38876156)

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