NM_001330195.2:c.3262+45366T>C

Variant names:

• chr14-79033507-T-C
• rs10146527
• NM_001330195.2:c.3262+45366T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330195.2(NRXN3):​c.3262+45366T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,876 control chromosomes in the GnomAD database, including 11,576 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 0.38 (11576 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 8 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3262+45366T>C		intron_variant	Intron 15 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3262+45366T>C		intron_variant	Intron 15 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57849 AN: 151758 Hom.: 11562 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.381 AC: 57903 AN: 151876 Hom.: 11576 Cov.: 32 AF XY: 0.376 AC XY: 27880 AN XY: 74222

African (AFR) AF: 0.437 AC: 18081 AN: 41420

American (AMR) AF: 0.487 AC: 7418 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1532 AN: 3470

East Asian (EAS) AF: 0.160 AC: 820 AN: 5132

South Asian (SAS) AF: 0.326 AC: 1569 AN: 4818

European-Finnish (FIN) AF: 0.217 AC: 2299 AN: 10578

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24892 AN: 67904

Other (OTH) AF: 0.394 AC: 833 AN: 2114

Alfa AF: 0.384 Hom.: 4904

Bravo AF: 0.406

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.7
DANN	Benign	0.82
PhyloP100		-0.23
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: rs10146527; hg19: chr14-79499850;