14-78777702-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330195.2(NRXN3):c.2045-25918A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,042 control chromosomes in the GnomAD database, including 34,340 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 0.61 (34340 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN3	NM_001330195.2	c.2045-25918A>G		intron_variant		ENST00000335750.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN3	ENST00000335750.7	c.2045-25918A>G		intron_variant		5	NM_001330195.2	P1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93212 AN: 151924 Hom.: 34339 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.613 AC: 93218 AN: 152042 Hom.: 34340 Cov.: 32 AF XY: 0.616 AC XY: 45802 AN XY: 74324

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.652

Alfa AF: 0.745 Hom.: 19995

Bravo AF: 0.598

Asia WGS AF: 0.559 AC: 1945 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	6.1
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs987644; hg19: chr14-79244045;