chr14-78231213-G-A

Position:

• chr14-78231213-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330195.2(NRXN3):​c.-703-11178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,116 control chromosomes in the GnomAD database, including 1,269 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 0.12 (1267 hom., cov: 32)
  • Exomes 𝑓: 0.31 (2 hom.)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.-703-11178G>A		intron_variant		ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.-703-11178G>A		intron_variant		5	NM_001330195.2	ENSP00000338349	P1
NRXN3	ENST00000634499.2	c.-703-11178G>A		intron_variant		5		ENSP00000488920

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18924 AN: 151970 Hom.: 1263 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.147

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.308 AC: 8 AN: 26 Hom.: 2 AF XY: 0.364 AC XY: 8 AN XY: 22

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.375

GnomAD4 genome AF: 0.125 AC: 18952 AN: 152090 Hom.: 1267 Cov.: 32 AF XY: 0.128 AC XY: 9523 AN XY: 74376

Gnomad4 AFR AF: 0.0879

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.140

Alfa AF: 0.129 Hom.: 1061

Bravo AF: 0.116

Asia WGS AF: 0.152 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.70
DANN	Benign	0.66

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: rs983795; hg19: chr14-78697556;