rs8006322

Variant names:

• chr14-79188669-G-A
• rs8006322
• NM_001330195.2:c.3262+200528G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330195.2(NRXN3):​c.3262+200528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,152 control chromosomes in the GnomAD database, including 6,205 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 0.26 (6205 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 2 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

LOC124903352 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.3262+200528G>A		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3262+200528G>A		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3274+200528G>A		intron	N/A	NP_001353355.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.3262+200528G>A		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2143+200528G>A		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000634499.2	TSL:5	c.3274+200528G>A		intron	N/A	ENSP00000488920.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40255 AN: 152034 Hom.: 6207 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.264 AC: 40242 AN: 152152 Hom.: 6205 Cov.: 32 AF XY: 0.258 AC XY: 19183 AN XY: 74356

African (AFR) AF: 0.138 AC: 5716 AN: 41534

American (AMR) AF: 0.229 AC: 3500 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3472

East Asian (EAS) AF: 0.115 AC: 592 AN: 5164

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4816

European-Finnish (FIN) AF: 0.228 AC: 2413 AN: 10586

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24213 AN: 67966

Other (OTH) AF: 0.304 AC: 643 AN: 2116

Alfa AF: 0.320 Hom.: 6007

Bravo AF: 0.259

Asia WGS AF: 0.157 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.47
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8006322; hg19: chr14-79655012;