Ust-Ishim is a sample identified from only a femur bone pulled out of eroding sand on the banks of the Irtysh River in western Siberia in 2008. Later analysis established that the bone belonged to a man estimated to have lived around 45,000 years ago. His genome is one of the earliest Upper Paleolithic WGS genomes.
Neither Clearly East- nor West Eurasian
What makes this sample particularly interesting is that he does not fall clearly into either the East or West Eurasian category. The original Fu et al. study study placed him before, or approximately at, the separation of subsequent eastern and western Eurasian populations, which include all modern Eurasian populations. Later graph modelling reached essentially the same conclusion; the best fit placed Ust-Ishim slightly towards the West Eurasian branch, but the uncertainty overlapped the East-West split.
This can also be tested with -statistics:

These tests show no significant excess affinity between Ust-Ishim and either Tianyuan or several Upper Paleolithic West Eurasian groups.
Shared Drift Between Ust-Ishim and Modern Populations

In an outgroup -statistic test, Native American groups like Surui and Karitiana seem to share the most drift with Ust-Ishim out of the modern populations shown. Below I will test whether this shared drift can be explained through Ancient North Eurasian ancestry alone.
Does Ancient North Eurasian Ancestry Explain the Signal?

Using Mal’ta and Afontova Gora as comparators suggests that these two ANE-related groups cannot fully explain the excess affinity observed with Surui and Karitiana. While these -statistics fall below the threshold used in some ancient-DNA studies, they point in the same direction and corroborate the broader pattern.
Replacing the ANE comparators with the previous groups, such as Kostenki, Tianyuan, and Sunghir, results in significant deviations even under this stricter threshold.
Conclusion
Ust-Ishim appears to occupy a position near the split between later West and East Eurasians. Nevertheless, Karitiana and Surui consistently show excess affinity to Ust-Ishim relative to several Upper Paleolithic Eurasian and modern groups. Comparisons with Mal’ta and Afontova Gora suggest that known Ancient North Eurasian ancestry can account for part of this tendency, but not obviously all of it.