In silico pathogenicity prediction of a novel MEFV gene variant identified in an Iranian healthy individual

Familial Mediterranean Fever (FMF) is characterized by recurrent fever and serositis symptoms. FMF occurs as aresult of pathogenic variants in Mediterranean fever (MEFV) gene [۱]. The aim of this study was to predict thepathogenicity of MEFV: c.۳۱۹TA (p.Ser۱۰۷Thr) variant that was recently identified in a Lurish healthy individualfrom Iran. This variant was reported in the Iranome project as a novel missense variant (http://www.iranome.ir/) [۲].We performed our analysis using ten in silico predictive tools including PANTHER PSEP (http://pantherdb.org/),PhD-SNPg (https://snps.biofold.org/phd-snpg/#), PROVEAN and SIFT (both available at:http://provean.jcvi.org/index.php), Mutation Taster (http://www.mutationtaster.org/), SNPs & GO(https://snps.biofold.org/snps-and-go/), FATHMM-XF (http://fathmm.biocompute.org.uk/fathmm-xf/), I-MutantDisease (http://gpcr.biocomp.unibo.it/cgi/predictors/I-Mutant۳.۰/I-Mutant۳.۰.cgi), PolyPhen-۲(http://genetics.bwh.harvard.edu/pph۲/), CADD (https://cadd.gs.washington.edu/).The results of our analysis were as follows: PANTHER PSEP (Not Available), PhD-SNPg (Benign), PROVEAN(Neutral), Mutation Taster (Polymorphism), SNPs & GO (Neutral), FATHMM-XF (Benign), I-Mutant Disease (NotAvailable), PolyPhen-۲ (Probably Damaging), CADD (score: ۱۵.۳۳), SIFT (Damaging). Therefore, MEFV: c.۳۱۹TA(p.Ser۱۰۷Thr) variant was pathogenic on only two out of ten tools. Given that our threshold in accepting a variant aspathogenic was its deleterious effects in seven or more in silico predictive tools, MEFV: c.۳۱۹TA (p.Ser۱۰۷Thr)variant was rejected as pathogenic. However, for its final classification, it is necessary to consider the other criteriaprovided by American College of Medical Genetics and Genomics (ACMG-AMP) guidelines [۳].

کلیدواژه ها:

FMF ، MEFV gene ، in silico analysis.