14-78396376-A-G

Position:

• chr14-78396376-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330195.2(NRXN3):​c.757+98516A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,190 control chromosomes in the GnomAD database, including 59,083 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 0.88 (59083 hom., cov: 33)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN3	NM_001330195.2	c.757+98516A>G		intron_variant		ENST00000335750.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN3	ENST00000335750.7	c.757+98516A>G		intron_variant		5	NM_001330195.2	P1

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133340 AN: 152072 Hom.: 59046 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.897

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

GnomAD4 genome AF: 0.877 AC: 133421 AN: 152190 Hom.: 59083 Cov.: 33 AF XY: 0.879 AC XY: 65415 AN XY: 74410

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.939

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.912

Gnomad4 NFE AF: 0.938

Gnomad4 OTH AF: 0.898

Alfa AF: 0.924 Hom.: 32294

Bravo AF: 0.872

Asia WGS AF: 0.828 AC: 2877 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs2192420; hg19: chr14-78862719;