14-79093215-A-G

Variant names:

• chr14-79093215-A-G
• rs2221299
• NM_001330195.2:c.3262+105074A>G

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+105074A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 152,274 control chromosomes in the GnomAD database, including 74,689 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 0.99 (74689 hom., cov: 31)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.988 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+105074A>G		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3262+105074A>G		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3274+105074A>G		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+105074A>G		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2143+105074A>G		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000634499.2	TSL:5	c.3274+105074A>G		intron	N/A	ENSP00000488920.2

Frequencies

GnomAD3 genomes AF: 0.990 AC: 150684 AN: 152156 Hom.: 74634 Cov.: 31

Gnomad AFR AF: 0.996

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.983

Gnomad FIN AF: 0.967

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.992

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

GnomAD4 genome AF: 0.990 AC: 150794 AN: 152274 Hom.: 74689 Cov.: 31 AF XY: 0.989 AC XY: 73642 AN XY: 74448

African (AFR) AF: 0.996 AC: 41390 AN: 41554

American (AMR) AF: 0.997 AC: 15255 AN: 15294

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3469 AN: 3470

East Asian (EAS) AF: 0.946 AC: 4888 AN: 5166

South Asian (SAS) AF: 0.982 AC: 4735 AN: 4820

European-Finnish (FIN) AF: 0.967 AC: 10262 AN: 10612

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67503 AN: 68038

Other (OTH) AF: 0.987 AC: 2087 AN: 2114

Alfa AF: 0.992 Hom.: 9294

Bravo AF: 0.993

Asia WGS AF: 0.954 AC: 3317 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	0.99
DANN	Benign	0.54
PhyloP100		-0.27
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: rs2221299; hg19: chr14-79559558;