# Multiple Genetic Rare Variants in Autism Spectrum Disorders: A Single-Center Targeted NGS Study
## 3 Results
### Variants Already Associated with Autism  
We found 8 variants that were already described in the literature and associated with autism (Table 7). \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Patient** & **Gene** & \begin{tabular}{c} **Gene** \\ **Score** \\ \end{tabular} & **Variant** & **Inheritance** & **Predictions** & **Reference** & \begin{tabular}{c} **Aliele Frequency** \\ **(GnomAD)** \\ \end{tabular} \\ \hline r.g.74126 & FAT1 & 4 & \begin{tabular}{c} c.12653 A\textgreater{}G, \\ p.Asp4218 Gly \\ \end{tabular} & Mother & \begin{tabular}{c} unknown (S), \\ Possibly \\ damaging (P) \\ \end{tabular} & \begin{tabular}{c} [PERSON] et al., \\ 2014 [23] \\ \end{tabular} & 0.01 (1/100) (f) \\ H.S.M. & TSC1 & S & \begin{tabular}{c} c.1960 C\textgreater{}G, \\ p.Gln654 Glu \\ \end{tabular} & Mother & \
\begin{tabular}{c} Tolerated (S), \\ Benign (P) \\ \end{tabular} &
\begin{tabular}{c} [PERSON] et al., \\ 2012 [33] \\ \end{tabular} & 0.0007 (1/1400) (\({}^{\circ}\)) \\ \hline \hline \end{tabular}
\end{table} 
Table 6: _Cont._  
Figure 1: Graphic representation of segregation analysis data on all 101 inherited variants (**a**). Graphic representation of segregation analysis data on inherited extremely rare variants (**b**). Graphic representation of segregation analysis data on inherited deleterious variants (**c**). We found 2 variants with a frequency between 0.02% and 0.1% (*) and 6 variants with a frequency between 0.2% and 1.0% (f). All these variants are not extremely rare. As described in Table 6, the variant, c.2242C>A (p.Leu748 Ile), in the NRXN1 gene was already found in 2 patients with severe autism and paternal transmission [26; 27]. In our patient (O12/11), we found this variant, inherited from the mother, together with another frequent variant in the same gene, inherited from the father, plus three additional extremely rare variants in SOX5 (variant not present in GnomAD), CNTNAP2 (AF 0.003%), and CDKL5 (AF 0.013%), the first of which was inherited from the father and the other two from the mother. The transition, c.236G>A (p.Gly79 Glu), in MBD5 was first discovered by [PERSON] et al. (2011) [28] at a significantly higher frequency in patients than controls. In our patient ([PERSON]), we found this variant together with three extremely rare variants in TSC1 (variant not present in GnomAD), FAT1 (AF 0.002%), and SHANK3 (variant not present in GnomAD), as well as another three more frequent in SLIT3 (AF 0.02%), SCN2A (AF 0.4%), and ZEB2 (AF 0.2%). In this case, it was not possible to study the variant segregation in the family. The variant, c.5156C>T (p.Ser1719 Leu), in the RELN gene was first identified by [PERSON] et al. [29] in two families, whereas in our study, it was found in one patient (A14/06), with a paternal transmission, together with two other frequent variants in VPS13B (AF 0.9%) and RAI1 (AF 0.3%), the first of which was inherited from the mother and the second from the father, plus one rare variant in ZNF804A (AF 0.07%), inherited from the father, and two extremely rare variants in NRNX1 (not present in GnomAD) and NRNX3 (AF 0.005%), both inherited from the mother. The known Gly56 Ala mutation (c.167G>C) in the serotonin transporter, SERT (or 5-HTT), encoded by the SLC6A4 gene, causes an increased serotonin reuptake and has been associated with autism and rigid-compulsive behavior [30; 31]. In our patient (D15/81), we found this variant, together with two other frequent variants in VPS13B (AF 0.85%) and