14-79531661-A-T

Variant names:

• chr14-79531661-A-T
• rs1424850
• NM_001330195.2:c.3444+64259A>T

Variant summary

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

The NM_001330195.2(NRXN3):​c.3444+64259A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,040 control chromosomes in the GnomAD database, including 6,986 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 0.28 (6986 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN3	NM_001330195.2	c.3444+64259A>T		intron_variant	Intron 16 of 20	ENST00000335750.7	NP_001317124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN3	ENST00000335750.7	c.3444+64259A>T		intron_variant	Intron 16 of 20	5	NM_001330195.2	ENSP00000338349.7

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42467 AN: 151922 Hom.: 6956 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.280 AC: 42537 AN: 152040 Hom.: 6986 Cov.: 32 AF XY: 0.280 AC XY: 20826 AN XY: 74338

African (AFR) AF: 0.452 AC: 18741 AN: 41442

American (AMR) AF: 0.201 AC: 3077 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1036 AN: 3466

East Asian (EAS) AF: 0.232 AC: 1201 AN: 5174

South Asian (SAS) AF: 0.353 AC: 1699 AN: 4812

European-Finnish (FIN) AF: 0.218 AC: 2307 AN: 10578

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13480 AN: 67976

Other (OTH) AF: 0.309 AC: 652 AN: 2108

Alfa AF: 0.226 Hom.: 567

Bravo AF: 0.283

Asia WGS AF: 0.302 AC: 1050 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.66
PhyloP100		0.64
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: rs1424850; hg19: chr14-79998004;