Genetic Variant NRXN3:c.2275+48166A>G (chr14-78858510-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001330195.2(NRXN3):c.2275+48166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 152,272 control chromosomes in the GnomAD database, including 334 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 0.046 ( 334 hom., cov: 32)

Consequence

NRXN3
NM_001330195.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.64

Publications

3 publications found

Variant links:

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

NRXN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.155 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NRXN3	NM_001330195.2	MANE Select	c.2275+48166A>G	intron	N/A	NP_001317124.1
NRXN3	NM_001366425.1		c.2275+48166A>G	intron	N/A	NP_001353354.1
NRXN3	NM_001366426.1		c.2287+48166A>G	intron	N/A	NP_001353355.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NRXN3	ENST00000335750.7	TSL:5 MANE Select	c.2275+48166A>G	intron	N/A	ENSP00000338349.7
NRXN3	ENST00000554719.5	TSL:1	c.1156+48166A>G	intron	N/A	ENSP00000451648.1
NRXN3	ENST00000556496.2	TSL:1	n.1592+54687A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0455

AC:

6924

AN:

152154

Hom.:

330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0281

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0487

Gnomad OTH

AF:

0.0340

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

GnomAD4 genome

AF:

0.0456

AC:

6939

AN:

152272

Hom.:

334

Cov.:

AF XY:

0.0457

AC XY:

3403

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0122

AC:

506

AN:

41562

American (AMR)

AF:

0.161

AC:

2451

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

107

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0292

AC:

141

AN:

4830

European-Finnish (FIN)

AF:

0.0232

AC:

247

AN:

10624

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0487

AC:

3309

AN:

68014

Other (OTH)

AF:

0.0331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

325

649

974

1298

1623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0497

Hom.:

124

Bravo

AF:

0.0531

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.069

(source)

DANN

Benign

0.68

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over