rs2202167

Variant names:

• chr14-79033282-C-A
• rs2202167
• NM_001330195.2:c.3262+45141C>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+45141C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,896 control chromosomes in the GnomAD database, including 11,503 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 0.38 (11503 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3262+45141C>A		intron_variant	Intron 15 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3262+45141C>A		intron_variant	Intron 15 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57659 AN: 151778 Hom.: 11493 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.380 AC: 57706 AN: 151896 Hom.: 11503 Cov.: 32 AF XY: 0.374 AC XY: 27765 AN XY: 74246

African (AFR) AF: 0.435 AC: 17991 AN: 41406

American (AMR) AF: 0.486 AC: 7405 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1527 AN: 3464

East Asian (EAS) AF: 0.161 AC: 832 AN: 5154

South Asian (SAS) AF: 0.313 AC: 1510 AN: 4820

European-Finnish (FIN) AF: 0.217 AC: 2301 AN: 10592

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.366 AC: 24858 AN: 67920

Other (OTH) AF: 0.391 AC: 824 AN: 2106

Alfa AF: 0.371 Hom.: 5958

Bravo AF: 0.405

Asia WGS AF: 0.259 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.35
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: rs2202167; hg19: chr14-79499625;