14-78714883-C-T

Position:

• chr14-78714883-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001330195.2(NRXN3):​c.1788C>T​(p.Thr596Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,614,000 control chromosomes in the GnomAD database, including 20,840 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 0.19 (3112 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17728 hom.)
• Consequence: NRXN3 NM_001330195.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.38

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-4.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.1788C>T	p.Thr596Thr	synonymous_variant	8/21	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.1788C>T	p.Thr596Thr	synonymous_variant	8/21	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28118 AN: 152046 Hom.: 3104 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.181

GnomAD3 exomes AF: 0.155 AC: 38875 AN: 251168 Hom.: 3725 AF XY: 0.161 AC XY: 21918 AN XY: 135748

Gnomad AFR exome AF: 0.303

Gnomad AMR exome AF: 0.0688

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.0702

Gnomad SAS exome AF: 0.264

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.147 AC: 214196 AN: 1461834 Hom.: 17728 Cov.: 35 AF XY: 0.151 AC XY: 109466 AN XY: 727218

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.0733

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.0687

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.185 AC: 28171 AN: 152166 Hom.: 3112 Cov.: 32 AF XY: 0.184 AC XY: 13671 AN XY: 74380

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.0691

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.181

Alfa AF: 0.153 Hom.: 2410

Bravo AF: 0.185

Asia WGS AF: 0.169 AC: 587 AN: 3478

EpiCase AF: 0.149

EpiControl AF: 0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.42
DANN	Benign	0.87

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: rs1004212; hg19: chr14-79181226; COSMIC: COSV59752848; COSMIC: COSV59752848;