Table 3.

Point based variant classification categories

Category	Point ranges
Pathogenic	≥ 10
Likely Pathogenic	6 – 9 ¥
Uncertain	0 – 5
Likely Benign	−1 – −6 ¥
Benign	≤ −7

^¥Operationally, the prior probability should be understood to be infinitesimally greater than 0.10. This has two effects. First, it makes the posterior probability of the ACMG likely pathogenic combining rules infinitesimally greater than 0.90, so that the likely pathogenic rules work properly. A specific value of 0.102 would have the added benefit that 7 points would meet the IARC likely pathogenic threshold of 0.95. Second, it enforces a requirement for some evidence of benign effect for sequence variants to be classified as likely benign. One could also argue that the point threshold for likely benign should really be −2. This would match the ACMG rule “Likely Benign (ii)” rather than the simple numerical requirement that the posterior probability be <0.10.