14-79473650-G-A

Position:

• chr14-79473650-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.3444+6248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,124 control chromosomes in the GnomAD database, including 3,400 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 0.21 (3400 hom., cov: 33)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

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=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3444+6248G>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.3444+6248G>A		intron_variant		5	NM_001330195.2	ENSP00000338349	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31470 AN: 152006 Hom.: 3398 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.207 AC: 31476 AN: 152124 Hom.: 3400 Cov.: 33 AF XY: 0.205 AC XY: 15222 AN XY: 74378

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.180

Alfa AF: 0.204 Hom.: 3228

Bravo AF: 0.206

Asia WGS AF: 0.0660 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.62

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: rs17109256; hg19: chr14-79939993;