# Multiple Genetic Rare Variants in Autism Spectrum Disorders: A Single-Center Targeted NGS Study
## 3 Results
### Most Frequently Mutated Genes  
We identified 9 genes that are more frequently mutated, compared to the others, with more than 5 variants found in each of them.  
We detected 12 variants in the FAT1 gene, with two in the same patient (F12/67), both of which were inherited from the father (Tables 3 and 8); 12 variants in the VPS13B gene, with one shared by two patients (Tables 3 and 7), two present in the same patient (A15/18), and another two present in the same patient (D10/14), for whom studying the segregation in the families was not possible (Tables 3 and 8); 6 variants in ANK2 and RAI1 (in RAI1 three variants are the same) (Tables 3 and 7); 5 variants in SHANK3, ANKRD11, CSMD1, DLGAP2, and ZNF804A, with two (in ZNF804 gene) in the same patient, both of which were naturally transmitted (Tables 3 and 8).  
We used a binomial test to compare the mutational frequencies of these 9 genes in our cohort, with the frequencies in the GnomAD population (as shown in Table 3). For all these 9 genes, we noted significantly increased frequencies of rare variants in our study population. The results indicate that the frequency of mutation in all the genes we studied is higher than expected (1-tailed exact \(p<0.0001\)).  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline
**Gene** & **SFARI Score** & **Variant** & **Chr Position** & **Predictions** & **GnomAD** & **Patient** & **Transmission** \\ \hline \multirow{3}{*}{ZNF804A} & \multirow{3}{*}{3} & c.735 & \multirow{3}{*}{2:185,800,857} & \multirow{3}{*}{S/, P/} & 0.0005 & \multirow{3}{*}{G14/62} & \multirow{3}{*}{Maternal} \\  & & & & & & & \\  & & & & & & & \\  & & & & & & & \\ \hline \multirow{3}{*}{VPS13B} & \multirow{3}{*}{S} & c.611A\(>\)G; & \multirow{3}{*}{8:100,123,356} & S tolerated, P & \multirow{3}{*}{0.0009 (1/11,000)} & \multirow{3}{*}{A15/18} & \multirow{3}{*}{Unknown} \\  & & p.Asn204 Ser & & & & & \\  & & & & & & & \\  & & & & & & & \\ \hline \multirow{3}{*}{GNA14} & \multirow{3}{*}{6} & c.6304C\(>\)T; & \multirow{3}{*}{8:100,711,935} & S tolerated, P & \multirow{3}{*}{0.00008 (1/125,000)} & \multirow{3}{*}{A15/18} & \multirow{3}{*}{Unknown} \\  & & p.Arg2102 Cys & & & & & \\  & & & & & & \\ \hline \multirow{3}{*}{GNA14} & \multirow{3}{*}{6} & c.215C\(>\)T; & \multirow{3}{*}{9:80,144,079} & S tolerated, P & \multirow{3}{*}{0.0013 (1/750)} & \multirow{3}{*}{E11/61} & \multirow{3}{*}{Unknown} \\  & & p.Thr72 Met & & & & & \\  & & & & & & \\ \hline \multirow{3}{*}{FAT1} & \multirow{3}{*}{4} & c.97C\(>\)T; & \multirow{3}{*}{9:80,262,613} & S deleterious, P & \multirow{3}{*}{0.005 (1/200)} & \multirow{3}{*}{E11/61} & \multirow{3}{*}{Unknown} \\  & & p.Arg33 Cys & & & & & \\ \hline \multirow{3}{*}{FAT1} & \multirow{3}{*}{4} & c.9457G\(>\)A; & \multirow{3}{*}{4:187,534,269} & S deleterious, P & \multirow{3}{*}{not present} & \multirow{3}{*}{F12/67} & \multirow{3}{*}{Paternal} \\  & & p.Asp3153 Asn & & & & & \\  & & & & & & \\  & & & & & & \\  & & & & & & \\ \hline \multirow{3}{*}{VPS13B} & \multirow{3}{*}{S} & c.7957G\(>\)A; & \multirow{3}{*}{4:187,539,783} & S deleterious, P & \multirow{3}{*}{0.0006 (1/1500)} & \multirow{3}{*}{F12/67} & \multirow{3}{*}{Paternal} \\  & & p.Gly2653 Ser & & & & & \\  & & & & & & \\  & & & & & & \\  & & & & & & \\  & & & & & & \\ \hline \multirow{3}{*}{VPS13B} & \multirow{3}{*}{S} & c.11270G\(>\)A; & \multirow{3}{*}{8:100,874,154} & S tolerated, P & \multirow{3}{*}{0.0017 (1/600)} & \multirow{3}{*}{D10/14} & \multirow{3}{*}{Unknown} \\  & & p.Arg375 Gln & & & & & \\  & & & & & & \\