Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia

Table 1 NRXN1 variants identified in this study

Chr	Position dbSNP ID	Ref	Val	Amino acid variant	Our cohort	iJGVDa	HGVDa	gnomAD^a	ClinVar	Tools for predicting the deleteriousness of missense variants
				NP_004792	MAF	MAF	MAF	MAF		PolyPhen-2	MutationTaster	REVEL^b	CADD^c
				NP_620072	MAF	MAF	MAF	MAF		PolyPhen-2	MutationTaster	REVEL^b	CADD^c
2	50091401	C	T	V1214I	1 SCZ	6/7100	4/2420	12/251454	–	0.245	29	0.242	22.1
2	rs752722196	C	T	V179I	8.9 × 10^{− 4}	8.4 × 10 ^{− 4}	1.7 × 10 ^{− 3}	4.8 × 10 ^{− 5}	–	Benign	Polymorphism	0.242	22.1
2	50091446	C	T	A1199T	2 ASD/1 SCZ	17/7086	10/2420	107/282828	Likely benign	0.087	58	0.233	16.98
2	rs201336161	C	T	A164T	2.7 × 10 ^{− 3}	2.4 × 10 ^{− 3}	4.1 × 10 ^{− 3}	3.8 × 10 ^{− 4}	Likely benign	Benign	Polymorphism	0.233	16.98
2	50236845	C	T	V1164I	1 ASD	2/7104	1/2054	12/282134	–	0.460	29	0.15	14.39
	rs201881725			V129I	8.9 × 10 ^{− 4}	2.8 × 10 ^{− 4}	4.9 × 10 ^{− 4}	4.3 × 10 ^{− 5}		Probably damaging	Polymorphism
2	50497646	G	A	R856W	1 SCZ	–	–	–	Uncertain	1.0	101	0.706	27.8
2	rs796052777	G	A	–	8.9 × 10 ^{− 4}	–	–	–	Significance	Probably damaging	Disease causing	0.706	27.8
2	50531259	T	C	D772G	1 ASD	–	–	1/248460	–	1.0	94	0.761	29.6
2	rs1457374261	T	C	–	8.9 × 10 ^{− 4}	–	–	4.0 × 10 ^{− 6}	–	Probably damaging	Disease causing	0.761	29.6
2	50531364	G	A	T737M	1 ASD/1 SCZ	–	–	2/247276	Uncertain	1.0	81	0.686	28.4
2	rs199970666	G	A	–	1.8 × 10 ^{− 3}			8.1 × 10 ^{− 6}	Significance	Probably damaging	Disease causing	0.686	28.4

Genomic position based on NCBI build GRCh38.p12 (Ensembl Transcript IDs ENST00000406316.6 and ENST00000342183.9). The amino acid position is based on NCBI reference sequences NP_004792 and NP_620072, respectively
Chr chromosome, dbSNP dbSNP build 151, Ref reference, Val variant, MAF minor allele frequency, SCZ schizophrenia, ASD autism spectrum disorders, iJGVD integrative Japanese Genome Variation Database, HGVD Human Genetic Variation Database, gnomAD Genome Aggregation Database, ClinVar NCBI ClinVar, PolyPhen-2 polymorphism phenotyping v.2, REVEL Rare Exome Variant Ensemble Learner, CADD Combined Annotation–Dependent Depletion v1.4
For details of each database, see Supplemental methods. None of the SNVs detected in our study were registered in the DECIPHER database
^aMinor allele count/total allele count
^bThe REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing
^cReference genome SNVs at the 10th-% of CADD scores are assigned to 10, top 1 to 20% and top 0.1 to 30%

ISSN: 1866-1955