14-78484862-G-A

Position:

• chr14-78484862-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BS1 BS2

The NM_001330195.2(NRXN3):​c.758-160258G>A variant causes a intron change. The variant allele was found at a frequency of 0.0112 in 152,200 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.011 (18 hom., cov: 33)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 4.26

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.12).
• BP6: Variant 14-78484862-G-A is Benign according to our data. Variant chr14-78484862-G-A is described in ClinVar as [Benign]. Clinvar id is 590907.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0112 (1707/152200) while in subpopulation NFE AF= 0.0161 (1098/68010). AF 95% confidence interval is 0.0154. There are 18 homozygotes in gnomad4. There are 843 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1707 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.758-160258G>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.758-160258G>A		intron_variant		5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1706 AN: 152082 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.00924

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0112 AC: 1707 AN: 152200 Hom.: 18 Cov.: 33 AF XY: 0.0113 AC XY: 843 AN XY: 74398

Gnomad4 AFR AF: 0.00291

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.00924

Gnomad4 NFE AF: 0.0161

Gnomad4 OTH AF: 0.0165

Alfa AF: 0.0135 Hom.: 3

Bravo AF: 0.0111

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autism Uncertain:1

Uncertain significance, no assertion criteria provided

research

Michaelson Lab, University of Iowa

Aug 01, 2018

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

NRXN3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Benign	0.70

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: rs117696080; hg19: chr14-78951205;