rs771275997

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_181303.2(NLGN3):c.435C>T(p.Asn145Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,207,995 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 108 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 2 hem., cov: 21)

Exomes 𝑓: 0.00025 ( 0 hom. 106 hem. )

Consequence

NLGN3
NM_181303.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.492

Publications

1 publications found

Variant links:

Genes affected

NLGN3 (HGNC:14289): (neuroligin 3) This gene encodes a member of a family of neuronal cell surface proteins. Members of this family may act as splice site-specific ligands for beta-neurexins and may be involved in the formation and remodeling of central nervous system synapses. Mutations in this gene may be associated with autism and Asperger syndrome. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Oct 2009]

NLGN3 Gene-Disease associations (from GenCC):

autism, susceptibility to, X-linked 1
Inheritance: Unknown, XL Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: MODERATE Submitted by: Illumina, ClinGen

NLGN3 links:

ENSG00000228427 (HGNC:):

ENSG00000228427 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant X-71148184-C-T is Benign according to our data. Variant chrX-71148184-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211677.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BP7

Synonymous conserved (PhyloP=0.492 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 2 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN3	NM_181303.2 link	c.435C>T	p.Asn145Asn	synonymous_variant	Exon 2 of 8	ENST00000358741.4	NP_851820.1	Q9NZ94-1X5DNV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN3	ENST00000358741.4 link	c.435C>T	p.Asn145Asn	synonymous_variant	Exon 2 of 8	5	NM_181303.2	ENSP00000351591.4		Q9NZ94-1
NLGN3	ENST00000685718.1 link	n.435C>T		non_coding_transcript_exon_variant	Exon 2 of 8			ENSP00000510514.1		A0A8I5QJU7

Frequencies

GnomAD3 genomes

AF:

0.000117

AC:

AN:

111517

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000948

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000749

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000170

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000169

AC:

AN:

183430

AF XY:

0.000250

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000977

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000246

AC:

270

AN:

1096424

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

106

AN XY:

361834

show subpopulations

African (AFR)

AF:

0.0000759

AC:

AN:

26366

American (AMR)

AF:

0.00

AC:

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19379

East Asian (EAS)

AF:

0.00

AC:

AN:

30190

South Asian (SAS)

AF:

0.00128

AC:

AN:

54106

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40517

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.000208

AC:

175

AN:

840500

Other (OTH)

AF:

0.000434

AC:

AN:

46031

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000117

AC:

AN:

111571

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33753

show subpopulations

African (AFR)

AF:

0.0000326

AC:

AN:

30701

American (AMR)

AF:

0.0000946

AC:

AN:

10566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3545

South Asian (SAS)

AF:

0.000751

AC:

AN:

2663

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000170

AC:

AN:

53025

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000144

EpiCase

AF:

0.000491

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 14, 2014

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

NLGN3-related disorder

Benign:1

Dec 05, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NLGN3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.8

(source)

DANN

Benign

0.79

PhyloP100

0.49

Mutation Taster

=98/2

polymorphism

(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.

rs771275997

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over