chr14-79518375-C-A

Variant names:

• chr14-79518375-C-A
• rs10083466
• NM_001330195.2:c.3444+50973C>A

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+50973C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,856 control chromosomes in the GnomAD database, including 15,201 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 0.39 (15201 hom., cov: 32)
• Consequence: NRXN3 NM_001330195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330195.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	NM_001330195.2	MANE Select	c.3444+50973C>A		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3444+50973C>A		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3456+50973C>A		intron	N/A	NP_001353355.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.3444+50973C>A		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2325+50973C>A		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000428277.6	TSL:1	c.429+50973C>A		intron	N/A	ENSP00000394426.2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58560 AN: 151742 Hom.: 15151 Cov.: 32

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.386 AC: 58662 AN: 151856 Hom.: 15201 Cov.: 32 AF XY: 0.385 AC XY: 28599 AN XY: 74198

African (AFR) AF: 0.731 AC: 30287 AN: 41448

American (AMR) AF: 0.265 AC: 4045 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1241 AN: 3472

East Asian (EAS) AF: 0.433 AC: 2237 AN: 5164

South Asian (SAS) AF: 0.499 AC: 2401 AN: 4810

European-Finnish (FIN) AF: 0.225 AC: 2365 AN: 10488

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14842 AN: 67918

Other (OTH) AF: 0.409 AC: 863 AN: 2110

Alfa AF: 0.275 Hom.: 3586

Bravo AF: 0.400

Asia WGS AF: 0.514 AC: 1785 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.16
PhyloP100		-0.020
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: rs10083466; hg19: chr14-79984718;