rs17107542

Variant names:

• chr14-78424708-T-A
• rs17107542
• NM_001330195.2:c.757+126848T>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.757+126848T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,218 control chromosomes in the GnomAD database, including 1,048 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 0.10 (1048 hom., cov: 33)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• 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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.757+126848T>A		intron	N/A	NP_001317124.1	A0A0A0MR89
	NRXN3	NM_001366425.1		c.757+126848T>A		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.769+124017T>A		intron	N/A	NP_001353355.1	A0A0U1RQC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.757+126848T>A		intron	N/A	ENSP00000338349.7	A0A0A0MR89
	NRXN3	ENST00000554719.5	TSL:1	c.-363+20830T>A		intron	N/A	ENSP00000451648.1	Q9Y4C0-3
	NRXN3	ENST00000634499.2	TSL:5	c.769+124017T>A		intron	N/A	ENSP00000488920.2	A0A0U1RQC5

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15368 AN: 152098 Hom.: 1038 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.0687

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.101 AC: 15411 AN: 152218 Hom.: 1048 Cov.: 33 AF XY: 0.103 AC XY: 7644 AN XY: 74440

African (AFR) AF: 0.173 AC: 7182 AN: 41508

American (AMR) AF: 0.158 AC: 2410 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 223 AN: 3470

East Asian (EAS) AF: 0.0686 AC: 356 AN: 5188

South Asian (SAS) AF: 0.0808 AC: 390 AN: 4826

European-Finnish (FIN) AF: 0.0808 AC: 857 AN: 10610

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0548 AC: 3725 AN: 68018

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0848 Hom.: 83

Bravo AF: 0.108

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.6
DANN	Benign	0.74
PhyloP100		1.0
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: rs17107542; hg19: chr14-78891051;