chr14-79775873-A-G

Variant names:

• chr14-79775873-A-G
• rs17764668
• NM_001330195.2:c.4015-29239A>G

Variant summary

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

The NM_001330195.2(NRXN3):​c.4015-29239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 152,220 control chromosomes in the GnomAD database, including 879 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 0.092 (879 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.4015-29239A>G		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3925-29239A>G		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.4027-29239A>G		intron	N/A	NP_001353355.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.4015-29239A>G		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2806-29239A>G		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000428277.6	TSL:1	c.1000-29239A>G		intron	N/A	ENSP00000394426.2

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14058 AN: 152102 Hom.: 878 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0953

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0673

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0923 AC: 14054 AN: 152220 Hom.: 879 Cov.: 32 AF XY: 0.0921 AC XY: 6851 AN XY: 74414

African (AFR) AF: 0.0245 AC: 1016 AN: 41542

American (AMR) AF: 0.0951 AC: 1454 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 616 AN: 3472

East Asian (EAS) AF: 0.0540 AC: 280 AN: 5186

South Asian (SAS) AF: 0.129 AC: 622 AN: 4826

European-Finnish (FIN) AF: 0.0673 AC: 714 AN: 10604

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8962 AN: 67986

Other (OTH) AF: 0.105 AC: 223 AN: 2116

Alfa AF: 0.124 Hom.: 601

Bravo AF: 0.0914

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		-0.84
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: rs17764668; hg19: chr14-80242216;