NM_001330195.2:c.2045-25918A>G

Variant names:

• chr14-78777702-A-G
• rs987644
• NM_001330195.2:c.2045-25918A>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.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
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.2045-25918A>G		intron_variant	Intron 8 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.2045-25918A>G		intron_variant	Intron 8 of 20	5	NM_001330195.2	ENSP00000338349.7

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

African (AFR) AF: 0.177 AC: 7350 AN: 41476

American (AMR) AF: 0.778 AC: 11891 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2701 AN: 3468

East Asian (EAS) AF: 0.630 AC: 3252 AN: 5166

South Asian (SAS) AF: 0.627 AC: 3009 AN: 4802

European-Finnish (FIN) AF: 0.771 AC: 8141 AN: 10558

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54503 AN: 67974

Other (OTH) AF: 0.652 AC: 1376 AN: 2112

Alfa AF: 0.744 Hom.: 22434

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
PhyloP100		-0.39
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: rs987644; hg19: chr14-79244045;