Table 1.

NMNAT1 (NM_022787.3) variants identified in association with cone and cone-rod dystrophy

Case ID	Ophthalmic phenotype	Genomic coordinate	Nucleotide change	Predicted amino-acid change	Population allele frequency	In silico: Align GVGD class, SIFT, MutTaster, PolyPhen-2, PhyloP, splicing affect	ACMG classification (supporting evidence)
Case 1	Cone dystrophy	Chr1:g.10035805G > A	c.[271G > A] homozygous	p.(Glu91Lys)	0.000004 (1/245660)	C0, T, D, B, Mod, N/A	Likely affects function (PM1; PM2; PM5; PP2)
Case 2	Cone-rod dystrophy	Chr1:g.10032184A > G	c.[53A > G]	p.(Asn18Ser)	0.000018 (5/276912)	C0, T, D, B, Mod, N/A	Affects function (PS1; PM1; PM2; PM3; PP2)
		Chr1:g.10042688G > A	c.[769G > A]	p.(Glu257Lys)	0.0006968 (193/276988)	C0, T, D, B, Mod, N/A	Affects function (PS1; PM1; PM2; PM3; PP2)

The variants described are located in the nicotinate-nucleotide adenylyltransferase protein domain and are heterozygous unless otherwise stated. In silico calculations were generated using Alamut Visual version 2.8.2 (Interactive Biosoftware, France). Reference sequence Genome Build GRCh37(hg19). Population allele frequencies sourced from gnomAD (http://gnomad.broadinstitute.org/). In silico definitions: C0 = amino acid substitution is unlikely to have a functional affect; D = deleterious/damaging; T = tolerated; B = benign; Mod = moderately conserved nucleotide; N/A = no affect predicted on splicing. ACMG classification assigned using in silico, pedigree information and the literature available. Further information regarding the evidence criteria can be found in the ACMG guidelines [10]