Variant 2-50053311-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330078.2(NRXN1):c.4088C>T(p.Ala1363Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NRXN1
NM_001330078.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.04

Variant links:

Genes affected

NRXN1 (HGNC:8008): (neurexin 1) This gene encodes a single-pass type I membrane protein that belongs to the neurexin family. Neurexins are cell-surface receptors that bind neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the central nervous system. This complex is required for efficient neurotransmission and is involved in the formation of synaptic contacts. Three members of this gene family have been studied in detail and are estimated to generate over 3,000 variants through the use of two alternative promoters (alpha and beta) and extensive alternative splicing in each family member. Recently, a third promoter (gamma) was identified for this gene in the 3' region. Mutations in this gene are associated with Pitt-Hopkins-like syndrome-2 and may contribute to susceptibility to schizophrenia. [provided by RefSeq, Aug 2016]

NRXN1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17065758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN1	NM_001330078.2 linkuse as main transcript	c.4088C>T	p.Ala1363Val	missense_variant	21/23	ENST00000401669.7	NP_001317007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7 linkuse as main transcript	c.4088C>T	p.Ala1363Val	missense_variant	21/23	5	NM_001330078.2	ENSP00000385017	A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251130

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

.;T;.;.;.;.;.;.;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.17

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

.;.;.;N;.;.;.;.;.;.

MutationTaster

Benign

0.86

N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.33

.;N;N;N;N;.;N;.;N;.

REVEL

Benign

0.15

Sift

Benign

0.18

.;T;T;T;T;.;T;.;T;.

Sift4G

Benign

0.076

T;T;T;T;T;D;T;T;T;T

Polyphen

0.076

.;.;B;.;.;.;.;.;.;.

Vest4

0.24

MutPred

0.18

.;Gain of MoRF binding (P = 0.091);.;.;.;.;.;.;.;.;

MVP

0.26

MPC

0.79

ClinPred

0.40

GERP RS

5.5

Varity_R

0.13

gMVP

0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over