Expanding ACMG variant classification guidelines into a general framework

Table 3 “Gold-standard” GoF variants in PRSS1

Variant		gpAF in gnomAD^a	hspAF in gnomAD^a
Nucleotide change	Amino acid change	gpAF in gnomAD^a	hspAF in gnomAD^a
Triplication CNV		Absent
Duplication CNV		Absent
Double “gain-of-function” CNV		Absent
c.47C > T	p.Ala16Val	Absent [78]
c.49C > A	p.Pro17Thr	Absent
c.56A > C	p.Asp19Ala	Absent
c.62A > C	p.Asp21Ala	Absent
c.65A > G	p.Asp22Gly	Absent
c.68A > G	p.Lys23Arg	Absent
c.63_71dup	p.Lys23_Ile24insIleAspLys	Absent
c.86A > T	p.Asn29Ile	Absent
PRSS1-PRSS2 hybrid (gene conversion)	p.Asn29Ile + p.Asn54Ser	Absent
c.86A > C	p.Asn29Thr	Absent
PRSS1-PRSS2 hybrid (gene conversion)	p.Asn29Ile + p.Asn54Ser	Absent
c.116 T > C	p.Val39Ala	Absent
c.276G > T	p.Lys92Asn	0.000007953	0.00006152 (African/African American)
c.364C > T	p.Arg122Cys	0.00001988	0.00003517 (non-Finnish European)
c.365G > A	p.Arg122His	0.00001194	0.00002639 (non-Finnish European)
c.365_366GC > AT	p.Arg122His	Absent

See the Genetic Risk Factors in Chronic Pancreatitis Database [38] for original genetic and functional analysis reports
GoF gain-of-function, gpAF global population allele frequency, hspAF highest subpopulation allele frequency
^aIn accordance with gnomAD v2.1.1 or SVs v2.1 (https://gnomad.broadinstitute.org/) [74]

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