rs117696080

Variant names:

• chr14-78484862-G-A
• rs117696080
• NM_001330195.2:c.758-160258G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1707 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330195.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.758-160258G>A		intron	N/A	NP_001317124.1	A0A0A0MR89
	NRXN3	NM_001366425.1		c.758-160258G>A		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.770-160258G>A		intron	N/A	NP_001353355.1	A0A0U1RQC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.758-160258G>A		intron	N/A	ENSP00000338349.7	A0A0A0MR89
	NRXN3	ENST00000554719.5	TSL:1	c.-363+80984G>A		intron	N/A	ENSP00000451648.1	Q9Y4C0-3
	NRXN3	ENST00000634499.2	TSL:5	c.770-160258G>A		intron	N/A	ENSP00000488920.2	A0A0U1RQC5

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

African (AFR) AF: 0.00291 AC: 121 AN: 41524

American (AMR) AF: 0.0141 AC: 215 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4816

European-Finnish (FIN) AF: 0.00924 AC: 98 AN: 10602

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0161 AC: 1098 AN: 68010

Other (OTH) AF: 0.0165 AC: 35 AN: 2116

Alfa AF: 0.0152 Hom.: 30

Bravo AF: 0.0111

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autism (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Benign	0.70
PhyloP100		4.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs117696080; hg19: chr14-78951205;