Bucking the trend, Syn’s tone is actually VERY high gain. A lot of guys use high gain amps, but keep the gain itself pretty low. Syn, as near as I can tell, pushes the gain pretty hard. That adds a lot of natural compression, which can account for the smoothness of the overall tone.
A lot of guys will say “scoop the mids,” meaning that if you set the bass and treble at 5 (noon) or higher, you’d set the mids down to 2 or so. Think Dime here, when you do that. Dime is awesome, but Syn doesn’t sound like Dime. He doesn’t scoop out the mids much.
Start with “all 5s(all noon) on your gain and tone knobs on the amp. Unless it’s a super high-gain modern amp, like a 5150 or and Engl, you’ll want to move the gain to 9 or 10. With a high-gain amp, maybe start with 6 or 7 out of ten.
Then just start sweeping the tone knobs to get a feel for what they change, and then tune your tone to taste.