NM_001330195.2:c.4093+16160C>T

Variant names:

• chr14-79821350-C-T
• rs2223033
• NM_001330195.2:c.4093+16160C>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.4093+16160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,002 control chromosomes in the GnomAD database, including 7,392 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 0.30 (7392 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.4093+16160C>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.4093+16160C>T		intron_variant	Intron 20 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45280 AN: 151884 Hom.: 7384 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.298 AC: 45306 AN: 152002 Hom.: 7392 Cov.: 32 AF XY: 0.303 AC XY: 22477 AN XY: 74304

African (AFR) AF: 0.162 AC: 6713 AN: 41480

American (AMR) AF: 0.423 AC: 6463 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1852 AN: 5152

South Asian (SAS) AF: 0.296 AC: 1422 AN: 4812

European-Finnish (FIN) AF: 0.386 AC: 4079 AN: 10572

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22835 AN: 67932

Other (OTH) AF: 0.296 AC: 625 AN: 2110

Alfa AF: 0.312 Hom.: 1014

Bravo AF: 0.298

Asia WGS AF: 0.317 AC: 1102 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.54
PhyloP100		-0.65
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: rs2223033; hg19: chr14-80287693;