14-78471334-C-A

Position:

• chr14-78471334-C-A

Variant summary

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

The NM_001330195.2(NRXN3):​c.757+173474C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.093 (7 hom., cov: 0)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.757+173474C>A		intron_variant		ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.757+173474C>A		intron_variant		5	NM_001330195.2	ENSP00000338349	P1

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 961 AN: 10332 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0929 AC: 960 AN: 10330 Hom.: 7 Cov.: 0 AF XY: 0.0877 AC XY: 448 AN XY: 5110

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.0740

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0155

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0384

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.113

Alfa AF: 0.850 Hom.: 58015

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.22
DANN	Benign	0.33

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: rs7157669; hg19: chr14-78937677; COSMIC: COSV73577932;