14-79691453-G-A

Variant names:

• chr14-79691453-G-A
• rs2160919
• NM_001330195.2:c.3617-720G>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.3617-720G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,816 control chromosomes in the GnomAD database, including 10,072 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 0.31 (10072 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 6 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

ENSG00000258637 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 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.3617-720G>A		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3617-6177G>A		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3629-720G>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.3617-720G>A		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2498-6177G>A		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000428277.6	TSL:1	c.602-720G>A		intron	N/A	ENSP00000394426.2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47245 AN: 151696 Hom.: 10042 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.312 AC: 47325 AN: 151816 Hom.: 10072 Cov.: 32 AF XY: 0.310 AC XY: 23002 AN XY: 74158

African (AFR) AF: 0.603 AC: 24966 AN: 41410

American (AMR) AF: 0.197 AC: 2996 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3466

East Asian (EAS) AF: 0.354 AC: 1813 AN: 5120

South Asian (SAS) AF: 0.378 AC: 1818 AN: 4808

European-Finnish (FIN) AF: 0.137 AC: 1443 AN: 10556

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12415 AN: 67912

Other (OTH) AF: 0.303 AC: 639 AN: 2108

Alfa AF: 0.227 Hom.: 15749

Bravo AF: 0.329

Asia WGS AF: 0.399 AC: 1389 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0090
DANN	Benign	0.35
PhyloP100		-2.4
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: rs2160919; hg19: chr14-80157796;