rs8019381

Positions:

• chr14-79854240-T-C

Variant summary

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

The NM_001330195.2(NRXN3):​c.4094-7102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 693,374 control chromosomes in the GnomAD database, including 284,946 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 0.89 (60060 hom., cov: 31)
  • Exomes 𝑓: 0.91 (224886 hom.)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.4094-7102T>C		intron_variant		ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.4094-7102T>C		intron_variant		5	NM_001330195.2	ENSP00000338349	P1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 134976 AN: 151992 Hom.: 60023 Cov.: 31

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.866

GnomAD4 exome AF: 0.911 AC: 493184 AN: 541264 Hom.: 224886 Cov.: 7 AF XY: 0.911 AC XY: 231648 AN XY: 254396

Gnomad4 AFR exome AF: 0.830

Gnomad4 AMR exome AF: 0.930

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.939

Gnomad4 FIN exome AF: 0.925

Gnomad4 NFE exome AF: 0.912

Gnomad4 OTH exome AF: 0.911

GnomAD4 genome AF: 0.888 AC: 135066 AN: 152110 Hom.: 60060 Cov.: 31 AF XY: 0.890 AC XY: 66208 AN XY: 74372

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.942

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.902

Gnomad4 OTH AF: 0.867

Alfa AF: 0.898 Hom.: 25830

Bravo AF: 0.882

Asia WGS AF: 0.962 AC: 3331 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0090
DANN	Benign	0.35

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: rs8019381; hg19: chr14-80320583;