Your AC would tend to lose some of its cooling capacity as it would not have significant air changes on the portion of the house where the return is closed. It would also reduce the amount of air available across the indoor coil.
In my opinion where the supply vents are located is not as important as where the return air vents are located. the supply vents should be located towards the outer walls if possible. the return air vents should be located towards the center of the dwelling if possible. every effort should be made to get the return air vents as high as possible on the wall , if not in the ceiling.Remember you are trying to get the warm air back to the a-coil so it can be pumped outside through the refrigeration lines to the condensing unit. if the ductwork is used for heating also you should put some return air vents down low to get the cool air to the furnace. This is my personal opinion and may not be everyones.
Yes. If you want to know the specific airflow rate you can try to find the manufacturer and model of the fan on your HVAC unit. By closing off some air vents you are putting more strain on the fan (effectively increasing the static pressure it has to overcome). This will lower the total flowrate for your system, and require slightly more power to run, but not by much if you're only closing a small percentage of the total vents.
Air vents are placed based on the required cfm load calculation per room not necessarily set at specific square feet apart. But you need to make sure that supply and return air are not close to each other. Supply air vents should be placed close to outside walls and return air close to interior central walls.
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