14-79622137-G-A

Variant names:

• chr14-79622137-G-A
• rs221497
• NM_001330195.2:c.3445-41641G>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.3445-41641G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,054 control chromosomes in the GnomAD database, including 2,105 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 0.14 (2105 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563
• Publications: 9 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

ENSG00000259106 (HGNC:58616):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 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.3445-41641G>A		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3445-41641G>A		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3457-41641G>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.3445-41641G>A		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2326-41641G>A		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000428277.6	TSL:1	c.430-41641G>A		intron	N/A	ENSP00000394426.2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21774 AN: 151936 Hom.: 2107 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0850

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.143 AC: 21790 AN: 152054 Hom.: 2105 Cov.: 32 AF XY: 0.145 AC XY: 10767 AN XY: 74312

African (AFR) AF: 0.266 AC: 11021 AN: 41442

American (AMR) AF: 0.0863 AC: 1319 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3466

East Asian (EAS) AF: 0.160 AC: 823 AN: 5150

South Asian (SAS) AF: 0.121 AC: 584 AN: 4818

European-Finnish (FIN) AF: 0.125 AC: 1323 AN: 10566

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0850 AC: 5780 AN: 68002

Other (OTH) AF: 0.142 AC: 300 AN: 2114

Alfa AF: 0.105 Hom.: 4089

Bravo AF: 0.146

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.48
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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: rs221497; hg19: chr14-80088480;