rs12882679

Variant names:

• chr14-79380895-G-A
• rs12882679
• NM_001330195.2:c.3263-86326G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330195.2(NRXN3):​c.3263-86326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,990 control chromosomes in the GnomAD database, including 6,281 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6281 hom., cov: 31)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 5 publications found

Genes affected

NRXN3 (HGNC:8010): (neurexin 3) This gene encodes a member of a family of proteins that function in the nervous system as receptors and cell adhesion molecules. Extensive alternative splicing and the use of alternative promoters results in multiple transcript variants and protein isoforms for this gene, but the full-length nature of many of these variants has not been determined. Transcripts that initiate from an upstream promoter encode alpha isoforms, which contain epidermal growth factor-like (EGF-like) sequences and laminin G domains. Transcripts initiating from the downstream promoter encode beta isoforms, which lack EGF-like sequences. Genetic variation at this locus has been associated with a range of behavioral phenotypes, including alcohol dependence and autism spectrum disorder. [provided by RefSeq, Dec 2012]

NRXN3 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3263-86326G>A		intron_variant	Intron 15 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3263-86326G>A		intron_variant	Intron 15 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41458 AN: 151870 Hom.: 6276 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.298

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41471 AN: 151990 Hom.: 6281 Cov.: 31 AF XY: 0.273 AC XY: 20275 AN XY: 74282

African (AFR) AF: 0.152 AC: 6283 AN: 41464

American (AMR) AF: 0.377 AC: 5741 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3468

East Asian (EAS) AF: 0.164 AC: 844 AN: 5148

South Asian (SAS) AF: 0.279 AC: 1341 AN: 4812

European-Finnish (FIN) AF: 0.298 AC: 3147 AN: 10560

Middle Eastern (MID) AF: 0.283 AC: 82 AN: 290

European-Non Finnish (NFE) AF: 0.324 AC: 22009 AN: 67982

Other (OTH) AF: 0.295 AC: 624 AN: 2114

Alfa AF: 0.299 Hom.: 2888

Bravo AF: 0.274

Asia WGS AF: 0.230 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.44
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12882679; hg19: chr14-79847238;