1st International and 10th National Iranian Conference on Bioinformatics
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In silico pathogenicity evaluation of QDPR: c.135T>A (p.Asn45Lys) variant
Paper ID : 1382-ICB10
Authors:
Keivan Moradi *, Sahand Khamooshian
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
Abstract:
Genetic mutations occurred in the genes related to BH4 cofactor, including quinoid dihydropteridine reductase (QDPR), may lead to hyperphenylalaninemia (HPA). DHPR deficiency is caused by defects in the corresponding gene QDPR (1). In this study, we evaluated the pathogenicity of QDPR: c.135T>A (p.Asn45Lys) variant using ten in silico predictive tools including PANTHER PSEP, PhD-SNPg, PROVEAN, Mutation Taster, SNPs & GO, FATHMM-XF, I-Mutant Disease, PolyPhen-2, CADD, and SIFT. NM_000320.3 and P09417-1 were used as reference sequences. Except for PhD- SNPg, FATHMM-XF, and SNPs & GO, the other seven in silico tools predicted deleterious effects for this variant. QDPR: c.135T>A (p.Asn45Lys) variant had been reported recently for the first time in an Iranian patient with DHPR deficiency (in compound heterozygous form) (2). There were no reports of this variant in the literature as well as in the LOVD, HGMD, dbSNP, ClinVar, gnomAD, 1KGP, and BIOPKU public databases. In conclusion, with a threshold of deleterious effects in seven or more in silico predictive tools, QDPR: c.135T>A (p.Asn45Lys) variant could be accepted as a pathogenic variant. However, for its final classification, it is necessary to consider the other criteria provided by American College of Medical Genetics and Genomics (ACMG-AMP) guidelines (3).
Keywords:
DHPR deficiency; QDPR gene; In silico analysis
Status : Paper Accepted (Poster Presentation)