In frame 313 of the Zapruder film (which captures the exact moment of the head shot) you can see a trail of brain matter following the trajectory of the bullet out of Kennedy's head.
The following shows the Zapruder film (frames 311 to 316) in slow motion to see this frame in context.
By comparison, the following is a high speed photo of a .22 calibre bullet travelling from right to left through an apple. You can see a cluster of debris accompanying the bullet as it exits the apple.
The red arrow in the photo below indicates the trajectory of the brain matter following the bullet out of Kennedy's head.
The trajectory of the fatal bullet prior to impact is indicated by the red arrow below. When followed back to its source suggests the origin of the fatal bullet to be behind and just to the left of where Zapruder was standing.
That is consistent with the autopsy photo showing the top of Kennedy's head blown off. You can see the entry hole just above his ear and the exit area blasted out the top of his head. The entry hole is smaller than the exit hole which is to be expected from the physics involved.
The pattern of the tissue around the hole above Kennedy's right ear matches the pattern of the tissue of the apple around the entry point of the bullet in the high-speed photo below..
The bullet did not exit out the left side.
The bullet did not exit out the back of his head which it would have had he been shot from the front. Consider the fact that he was leaning somewhat forward at the moment of the head shot. The next photos show no exit hole at the back of his head which would be there had he been shot from the front.
The bullet did not exit out the front anywhere below the hairline.
The next photo shows the likely path of the bullet.
Those who claim the head shot came from the Book Depository have to explain the entry hole above his right ear and the large exit hole out the top of his head. To receive such a shot from behind he would have needed to be looking to the right with respect to the limousine and have his head tilted significantly to his left. Instead, at the moment of the head shot, he is leaning somewhat forward and somewhat to his left. The following image is the usual scenario for the head shot from the rear. It does not take into account the entry hole is above Kennedy's right ear.
If we look at frame 312, the last frame before the head shot, we see that his head is tilted slightly to his left and slightly forward toward Jacqueline.
This evidence taken together suggests the fatal head shot came from behind and to the left of where Zapruder was standing.
He was standing on one of the pedestals of the pergola shown below.
Gary Mack, Curator of The Sixth Floor Museum at Dealey Plaza stated, "Newman appeared on WFAA-TV in Dallas about 15-20 minutes after the shooting. He said the shots came from behind him, "up on the mall," or "up on the knoll." He goes on to say, "Careful study of the tape shows him forming his lips to make the "mmm" sound, not "nnn." And he did not say "grassy" at any time." (Link)
As you can see from the following photo taken moments after the fatal shooting, the initial impression of the witnesses was that the head shot had come from up on the mall. Moments after the shooting and the motorcade has sped away to the hospital, people are still frozen in place looking in the direction of the origin of the shot. Two are still laying on the ground taking cover and looking in that direction. Notice they are neither looking in the direction of the Book Depository nor in the direction of the grassy knoll but in the direction of the "mall".
So, the region in red is the location from where the fatal head shot was fired, not from the Book Depository nor from behind the picket fence of the grassy knoll.
This is a frame of the Orville Nix film taken across the street from Zapruder showing him filming (standing on the pedestal).
Further evidence comes from the Wiegman film:
It would be natural to turn the camera in the direction from which the cameraman thought the shot(s) originated. Hester, who arises to investigate at the 22 second point of the video, appears to think the fatal shot originated behind the pergola.
That location is consistent with the trajectory of the fatal head shot. The lowest horizontal opening in the pergola wall would allow for the shot to have the trajectory consistent with the track indicated by the Zapruder film.