"Is your home in the US?"
Well, there is no "best way", but it is surely a common, grammatically correct sentence. I can give you some other sentences: 请问您从哪里来？/請問您從哪裡來？Where are you from? (哪里/哪裡 can be replaced with 哪儿/哪兒, same meaning. 请问/請問 makes the sentence sound more polite.) 您打哪儿来？/您打哪兒來？(This sentence is more like spoken language, and maybe dialectical.)
More in detail:
你的家在美国。= Your home is in the US.
你的家在美国吗？= Is your home in the US? / Your home is in the US?
In English, a question has a different sentence structure or an added "do/does" or at least a raised pitch (Your home is in the US?).
In Chinese, the sentence structure is the same. And because Chinese is a tonal language, you can not go up with your pitch to mark a question, because that changes the meaning of words. You need to speak the right tones as if it was a normal sentence and then add ma 吗.
The best example for that is that foreigners often say the Chinese "Excuse me?" (请问 qǐngwèn) with a rising tone and end up saying "Please kiss!" (请吻 qǐngwěn). :o)