NM_001001890.2:c.30C>T (p.Ser10=) is a synonymous variant in exon 1 of RUNX1. SpliceAI predicts no significant splicing impact (max delta 0.03), supporting BP4 and BP7 at the supporting benign level per the RUNX1 MM-VCEP v3.1.0.

In gnomAD v4.1, c.30C>T is observed at an extremely low frequency (1/1,598,264 alleles; AF=6.26e-7), well below the VCEP PM2_Supporting threshold of ≤0.00005. All subpopulations satisfy the threshold, and the variant is absent from gnomAD v2.1.

ClinVar reports c.30C>T as Likely Benign, with expert panel review status from the ClinGen Myeloid Malignancy Variant Curation Expert Panel. No contradictory evidence supporting pathogenicity was identified in verified publications.

No functional studies, de novo occurrences, proband case data, or segregation evidence for c.30C>T were identified in any verified publication. All ClinVar-linked PMIDs are about unrelated topics (newborn screening policy statements) and do not mention RUNX1 or this variant.

Applying the RUNX1 MM-VCEP v3.1.0 point-based classification framework (Tavtigian et al. 2020): PM2_Supporting (+1), BP4 (-1), BP7 (-1). Total score: -1. This falls in the Likely Benign range (-6 to -1).