chr14-78365884-G-A

Variant names:

• chr14-78365884-G-A
• rs12887245
• NM_001330195.2:c.757+68024G>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+68024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,196 control chromosomes in the GnomAD database, including 777 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 0.090 (777 hom., cov: 33)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.757+68024G>A		intron_variant	Intron 4 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.757+68024G>A		intron_variant	Intron 4 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13729 AN: 152078 Hom.: 775 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.0708

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

GnomAD4 genome AF: 0.0903 AC: 13748 AN: 152196 Hom.: 777 Cov.: 33 AF XY: 0.0912 AC XY: 6785 AN XY: 74408

African (AFR) AF: 0.105 AC: 4362 AN: 41522

American (AMR) AF: 0.0987 AC: 1509 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1450 AN: 5164

South Asian (SAS) AF: 0.0659 AC: 318 AN: 4822

European-Finnish (FIN) AF: 0.0852 AC: 904 AN: 10608

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0712 AC: 4844 AN: 68014

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0747 Hom.: 639

Bravo AF: 0.0936

Asia WGS AF: 0.153 AC: 534 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.82
PhyloP100		-0.35

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: rs12887245; hg19: chr14-78832227;