M doesn't work
Usually when ads play, pressing M does nothing. It should mute the sound I guess, most of the time it does, seems it depends on keyboard focus, too? Higher success rate in fullscreen. Yes I know there's also a mute button.
So my suspicion was that it's nice for Twitch when you can't immediately mute the sound when ads start playing, so I press alt+f4 instead to get rid of the whole thing.