14-79437033-G-A

Variant names:

• chr14-79437033-G-A
• rs2370983
• NM_001330195.2:c.3263-30188G>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.3263-30188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,946 control chromosomes in the GnomAD database, including 38,641 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 0.70 (38641 hom., cov: 30)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 15 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 (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330195.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.3263-30188G>A		intron	N/A	NP_001317124.1	A0A0A0MR89
	NRXN3	NM_001366425.1		c.3263-30188G>A		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3275-30188G>A		intron	N/A	NP_001353355.1	A0A0U1RQC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.3263-30188G>A		intron	N/A	ENSP00000338349.7	A0A0A0MR89
	NRXN3	ENST00000554719.5	TSL:1	c.2144-30188G>A		intron	N/A	ENSP00000451648.1	Q9Y4C0-3
	NRXN3	ENST00000428277.6	TSL:1	c.248-30188G>A		intron	N/A	ENSP00000394426.2	Q9HDB5-4

Frequencies

GnomAD3 genomes AF: 0.705 AC: 106984 AN: 151828 Hom.: 38595 Cov.: 30

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.705 AC: 107090 AN: 151946 Hom.: 38641 Cov.: 30 AF XY: 0.701 AC XY: 52078 AN XY: 74254

African (AFR) AF: 0.865 AC: 35860 AN: 41446

American (AMR) AF: 0.721 AC: 11009 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2273 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2252 AN: 5128

South Asian (SAS) AF: 0.623 AC: 3003 AN: 4818

European-Finnish (FIN) AF: 0.650 AC: 6854 AN: 10552

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43498 AN: 67950

Other (OTH) AF: 0.712 AC: 1504 AN: 2112

Alfa AF: 0.661 Hom.: 54358

Bravo AF: 0.719

Asia WGS AF: 0.586 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		-0.26
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: rs2370983; hg19: chr14-79903376; COSMIC: COSV107258542;