rs17836262

Variant names:

• chr14-79664720-C-G
• rs17836262
• NM_001330195.2:c.3616+771C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-79664720-C-G
• chr14-79664720-C-T

Variant summary

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

The NM_001330195.2(NRXN3):​c.3616+771C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,188 control chromosomes in the GnomAD database, including 1,018 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 0.11 (1018 hom., cov: 33)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• 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

ENSG00000258637 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 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.3616+771C>G		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3616+771C>G		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3628+771C>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.3616+771C>G		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2497+771C>G		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000428277.6	TSL:1	c.601+771C>G		intron	N/A	ENSP00000394426.2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16553 AN: 152070 Hom.: 1017 Cov.: 33

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.109 AC: 16569 AN: 152188 Hom.: 1018 Cov.: 33 AF XY: 0.107 AC XY: 7973 AN XY: 74402

African (AFR) AF: 0.0804 AC: 3339 AN: 41536

American (AMR) AF: 0.106 AC: 1622 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3472

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5154

South Asian (SAS) AF: 0.104 AC: 502 AN: 4822

European-Finnish (FIN) AF: 0.102 AC: 1084 AN: 10606

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9025 AN: 68000

Other (OTH) AF: 0.116 AC: 246 AN: 2116

Alfa AF: 0.0587 Hom.: 58

Bravo AF: 0.107

Asia WGS AF: 0.0660 AC: 229 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.1
DANN	Benign	0.65
PhyloP100		0.36
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: rs17836262; hg19: chr14-80131063;