rs760288

Variant names:

• chr14-79840587-C-T
• rs760288
• NM_001330195.2:c.4094-20755C>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.4094-20755C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,032 control chromosomes in the GnomAD database, including 44,901 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 0.77 (44901 hom., cov: 31)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.4094-20755C>T		intron_variant	Intron 20 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.4094-20755C>T		intron_variant	Intron 20 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116365 AN: 151914 Hom.: 44863 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.766 AC: 116455 AN: 152032 Hom.: 44901 Cov.: 31 AF XY: 0.771 AC XY: 57255 AN XY: 74304

African (AFR) AF: 0.714 AC: 29578 AN: 41444

American (AMR) AF: 0.789 AC: 12050 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2355 AN: 3464

East Asian (EAS) AF: 0.906 AC: 4678 AN: 5166

South Asian (SAS) AF: 0.820 AC: 3953 AN: 4822

European-Finnish (FIN) AF: 0.848 AC: 8968 AN: 10570

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52549 AN: 67980

Other (OTH) AF: 0.725 AC: 1534 AN: 2116

Alfa AF: 0.776 Hom.: 5697

Bravo AF: 0.757

Asia WGS AF: 0.845 AC: 2934 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.98
DANN	Benign	0.71
PhyloP100		-0.23
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: rs760288; hg19: chr14-80306930;