rs9323675

Variant names:

• chr14-79668288-G-A
• rs9323675
• NM_001330195.2:c.3616+4339G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-79668288-G-A
• chr14-79668288-G-C
• chr14-79668288-G-T

Variant summary

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

The NM_001330195.2(NRXN3):​c.3616+4339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,914 control chromosomes in the GnomAD database, including 8,926 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 0.26 (8926 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 1 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

ENSG00000258637 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3616+4339G>A		intron_variant	Intron 17 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3616+4339G>A		intron_variant	Intron 17 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39650 AN: 151794 Hom.: 8894 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.262 AC: 39726 AN: 151914 Hom.: 8926 Cov.: 32 AF XY: 0.260 AC XY: 19320 AN XY: 74236

African (AFR) AF: 0.605 AC: 25074 AN: 41438

American (AMR) AF: 0.141 AC: 2153 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 875 AN: 3466

East Asian (EAS) AF: 0.395 AC: 2026 AN: 5126

South Asian (SAS) AF: 0.204 AC: 981 AN: 4810

European-Finnish (FIN) AF: 0.127 AC: 1338 AN: 10560

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.0980 AC: 6657 AN: 67948

Other (OTH) AF: 0.248 AC: 524 AN: 2112

Alfa AF: 0.151 Hom.: 3922

Bravo AF: 0.281

Asia WGS AF: 0.338 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.51
DANN	Benign	0.22
PhyloP100		-2.0
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: rs9323675; hg19: chr14-80134631;