The boxed handstamp with REGISTERED
and the blank opening is a US registry marking. It was most likely applied either at Seattle, WA, either the main PO or Station F.
I am working from memory, but sometime around the start of the 20th century, countries in Europe began to prepare closed registered pouches for destinations in the US other than New York City, which was still the primary point of entry for 80% of all registered mail entering the US. The pouches were sent directly from New York to the alternate distribution Post Offices. The primary motivation was to reduce the workload at the New York Registry Division.
If I am remembering correctly on this, Chicago was one of these alternate destinations, so Chicago would receive these closed pouches, and redistribute the registered mail to other destinations in the Mid West and West Coast. Your letter received the two Double Circle markings (OCT 17, 1912) transit marking at Chicago on the reverse, and then the letter was transferred to another closed pouch and sent to Seattle. When received at Seattle, the pouch was opened, the clerk applied the double circle Seattle arrival markings (OCT 21) on the reverse.
It looks like the letter was then next sent to the Seattle, Station F, office for delivery, and here was most likely the source of the boxed REGISTERED marking. On the reverse there is a very faint double circle marking, which reads "SEATTLE, (STA. F) WASHINGTON", also dated Oct 21, 1912.
The two hand stamped numbers on the face are also Seattle markings. The smaller number, 50332
, was added for recording the cover when first received received at Station F, and given to the mail carrier for delivery at the original address: 213 Nickerson Ave.
It could not be delivered, but the mail carrier apparently received a corrected address, i.e, at 2608 Mayfair Ave, which is also also near Station F. There is a red pencil/crayon marking with this corrected address.
The Official Postal Guide
for July 1912 shows the location of Station F at 3422 Fremont Ave, Seattle, WA. The two delivery addresses are both nearby.
From Google maps:
The registry clerk at the Station F office then struck out the original number with a blue pencil, and applied the second number, 50462
, where it was given to another carrier, and apparently delivered successfully to the Mayfair address.
Each time a registered changed hands for a subsequent delivery attempt, it was given a new number to show which carrier took possession of the letter on each occasion. This provided positive tracking information in the event there was a later question regarding delivery.
Corrections to my analysis, or other interpretations invited.