chr14-79575283-C-A

Variant names:

• chr14-79575283-C-A
• rs221417
• NM_001330195.2:c.3445-88495C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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.

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.3445-88495C>A		intron	N/A	NP_001317124.1
	NRXN3	NM_001366425.1		c.3445-88495C>A		intron	N/A	NP_001353354.1
	NRXN3	NM_001366426.1		c.3457-88495C>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.3445-88495C>A		intron	N/A	ENSP00000338349.7
	NRXN3	ENST00000554719.5	TSL:1	c.2326-88495C>A		intron	N/A	ENSP00000451648.1
	NRXN3	ENST00000428277.6	TSL:1	c.430-88495C>A		intron	N/A	ENSP00000394426.2

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

African (AFR) AF: 0.212 AC: 8795 AN: 41430

American (AMR) AF: 0.0580 AC: 886 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0771 AC: 267 AN: 3464

East Asian (EAS) AF: 0.163 AC: 839 AN: 5160

South Asian (SAS) AF: 0.101 AC: 486 AN: 4812

European-Finnish (FIN) AF: 0.0241 AC: 255 AN: 10594

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.0539 AC: 3664 AN: 67990

Other (OTH) AF: 0.0954 AC: 201 AN: 2108

Alfa AF: 0.0565 Hom.: 189

Bravo AF: 0.110

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.71
PhyloP100		1.7
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: rs221417; hg19: chr14-80041626;