14-79169668-C-T

Variant names:

• chr14-79169668-C-T
• rs1531634
• NM_001330195.2:c.3262+181527C>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.3262+181527C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,056 control chromosomes in the GnomAD database, including 4,306 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 0.23 (4306 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3262+181527C>T		intron_variant	Intron 15 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3262+181527C>T		intron_variant	Intron 15 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35192 AN: 151936 Hom.: 4305 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.231 AC: 35188 AN: 152056 Hom.: 4306 Cov.: 32 AF XY: 0.228 AC XY: 16962 AN XY: 74338

African (AFR) AF: 0.208 AC: 8611 AN: 41486

American (AMR) AF: 0.190 AC: 2897 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1552 AN: 3472

East Asian (EAS) AF: 0.112 AC: 580 AN: 5174

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4814

European-Finnish (FIN) AF: 0.164 AC: 1740 AN: 10592

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17832 AN: 67940

Other (OTH) AF: 0.256 AC: 541 AN: 2110

Alfa AF: 0.252 Hom.: 6573

Bravo AF: 0.231

Asia WGS AF: 0.182 AC: 636 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	5.8
DANN	Benign	0.58
PhyloP100		0.61
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: rs1531634; hg19: chr14-79636011;