Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001879944 | SCV002185270 | uncertain significance | not provided | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with serine at codon 146 of the ASNS protein (p.Phe146Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ASNS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002265967 | SCV002547676 | uncertain significance | not specified | 2022-05-17 | criteria provided, single submitter | clinical testing | Variant summary: ASNS c.437T>C (p.Phe146Ser) results in a non-conservative amino acid change located in the Glutamine amidotransferase type 2 domain (IPR017932) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250860 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.437T>C in individuals affected with Asparagine Synthetase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Service de Génétique Moléculaire, |
RCV001255847 | SCV001432471 | likely pathogenic | Congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome | no assertion criteria provided | clinical testing |