An upstate New York school employee has been charged with murdering her sister whose body was found in a river after a huge three-day search.

Jamie Busch, a 53-year-old middle school paraprofessional in Honeoye Falls, a village about 20 miles from Rochester, was charged Friday with second-degree murder for her sister Penny Busch, a 62-year-old mom of two last seen 12 days earlier.

What was expected to be “a simple, routine” Oct. 11 welfare check on Penny Busch instead sparked a manhunt after deputies “found a few things that were odd, out of the ordinary,” Monroe County Sheriff Todd Baxter told a news conference Friday.

It started with a huge hunt using police search dogs and drones around the missing mom’s eight-acre property, the sheriff said.

Police divers then found a body in the Genesee River in Rush three days after the search started. It was identified as Penny Busch on Friday.

“Investigators established significant evidence and probable cause to arrest her sister, Jamie Busch, for the murder,” the sheriff’s office said, without elaborating.

Baxter said the cause of death and motive “are something we are going to keep close to our chest” — but that “we believe this is an isolated incident between family members.”

However, police believe Jamie Busch strangled Penny then dumped her body in the river, and hid her phones in a Dunkin Donuts dumpster, according to court paperwork obtained by 13-WHAM.

The sheriff praised his “sharp deputies who determined this was more than just a check the welfare with an adult not home.”

“The investigators’ determination to find leads, locate the deceased in the river, and apprehend her sister for the murder is remarkable,” the sheriff said.

Jamie was placed on leave from her job as a middle school paraprofessional, according to a statement from the Honeoye Falls-Lima Central School District.

“We are shocked and saddened by the reports,” Superintendent Gene Mancuso wrote.

“Although we have never encountered a situation like this in our district, we are confident that, as a community, we will come together, support one another, and get through this difficult time.”

Penny was raised in Schenectady, and spent most of her time in Texas before she moved to Monroe County roughly a year ago, cops said.

She had two sisters, including Jamie, and left behind two children, according to police.

Jamie was charged with murder in the second degree and two counts of tampering with physical evidence and remanded to Monroe County Jail without bail, court records show.