rs221417

chr14-79575283-C-Achr14-79575283-C-Gchr14-79575283-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001330195.2(NRXN3):c.3445-88495C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,038 control chromosomes in the GnomAD database, including 1,198 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 (1198 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN3	NM_001330195.2	c.3445-88495C>A		intron_variant		ENST00000335750.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN3	ENST00000335750.7	c.3445-88495C>A		intron_variant		5	NM_001330195.2	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15471 AN: 151920 Hom.: 1199 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0771

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.0964

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

GnomAD4 genome AF: 0.102 AC: 15474 AN: 152038 Hom.: 1198 Cov.: 32 AF XY: 0.101 AC XY: 7494 AN XY: 74326

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.0580

Gnomad4 ASJ AF: 0.0771

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0241

Gnomad4 NFE AF: 0.0539

Gnomad4 OTH AF: 0.0954

Alfa AF: 0.0539 Hom.: 154

Bravo AF: 0.110

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	17
Dann	Benign	0.71

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: rs221417; hg19: chr14-80041626;