The same thing happened to me this year. I mailed my 2020 tax return in March 2021 with a payment check enclosed in the same envelope. My bank shows that they deposited my check within a couple of weeks after I sent it. Then in December I received a Notice CP80 from the IRS in the mail. This notice is used when they have received a payment, but have not received a tax return to go with the payment. The notice tells you to file your tax return today.
What the notice is telling him is that they have received the $123.45, and that they have credited it to his account. However, they have not received a 2020 tax return, so they don't know how much he owes for his 2020 taxes. The warning on the notice says that he needs to file this tax return, because if the credit is not applied to a particular tax return, it may eventually be forfeit.
Yes, it is stupid that the IRS deposited the check and lost the return that was in the same envelope, but that is apparently what happened to me, your uncle, and another user today. I'm guessing the IRS lost a large group of returns. I am grateful that the check was deposited and credited correctly.
To remedy this, he just needs to mail in a copy of your tax return again to the address shown on the notice. Hopefully he kept a copy of his return like he is supposed to, because if he didn't, he will have to recreate it.
There will be no penalty for this if he sent in his check before the tax due date, because the penalty is for paying late, not for filing late. Having said that, your uncle should get this done as soon as possible (the notice says "today"), because they are about to start receiving lots of 2021 tax returns, and there is great potential for more mistakes by the IRS, sadly.
When I sent in a full copy of my tax return in December, I included a letter stating that this was a duplicate tax return sent in response to a CP80 notice, and that the original was sent in last March. My hope is that if they somehow find and process my original return, they won't wonder why they got the return twice.