3D spatial systems: does CAD/CAM axis rotation have a zero reference?

I am attempting to write my own CAD/CAM software as an exercise. I am familiar with computer programming/3d-graphics programming (DirectX) but I'm not sure if the same conventions are used in CAD software. I am not very familiar with g-code, but there's different versions anyway so I'm not sure which version would be definitive or even most-common. I'm not planning on using g-code anyway, so I don't strictly need to hold to any existing conventions of it.

I understand the difference of right-handed vs left-handed coordinates, and I have found online that the positive rotation around an axis is clockwise, when viewing the axis from the origin point (and so the origin end of any >3rd axis would be the end opposite of the tool, or opposite of the work being held...? I like this explanation as it can be applied to any possible axis). What I am wondering is if the axis rotation has a zero-degrees reference point or not? This doesn't matter much if you are just using the software maybe, but it is a big factor in writing it.

In particular for greater-than-3-axis setups, it seems like such reference points would be required. The zero point would be the 'home switches' on the 4th and 5th axis in hardware, but how is that defined in the software?

Like for example: if you set the zero-degrees point of the x-axis rotation and the zero-degrees point of the y axis to each other, then if you rotate any line or plane on either axis to zero degrees, then it would be sitting "flat" with the x-y plane. Which makes a lot of sense IMO.

For the z-axis you could use either the x or the y axis, and I'm inclined to use the x-axis (so that anything rotated to zero degrees on the z-axis would be "directly facing" the observer) but it would be annoying to start coding on that and find out later it was not the convention.