NM_181303.2:c.20C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_181303.2(NLGN3):c.20C>T(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,206,182 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 77 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P7P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00023 ( 0 hom. 73 hem. )

Consequence

NLGN3
NM_181303.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:2

Conservation

PhyloP100: -0.190

Publications

3 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: XL, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023700029).

BS2

High Hemizygotes in GnomAd4 at 4 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181303.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLGN3	NM_181303.2	MANE Select	c.20C>T	p.Pro7Leu	missense	Exon 2 of 8	NP_851820.1	X5DNV3
NLGN3	NM_018977.4		c.20C>T	p.Pro7Leu	missense	Exon 2 of 7	NP_061850.2	Q9NZ94-2
NLGN3	NM_001166660.2		c.20C>T	p.Pro7Leu	missense	Exon 2 of 6	NP_001160132.1	X5D7L6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLGN3	ENST00000358741.4	TSL:5 MANE Select	c.20C>T	p.Pro7Leu	missense	Exon 2 of 8	ENSP00000351591.4	Q9NZ94-1
NLGN3	ENST00000374051.7	TSL:1	c.20C>T	p.Pro7Leu	missense	Exon 2 of 7	ENSP00000363163.3	Q9NZ94-2
NLGN3	ENST00000395855.7	TSL:1	c.20C>T	p.Pro7Leu	missense	Exon 2 of 5	ENSP00000379196.3	E7EVK0

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

111822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000976

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000358

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000123

AC:

AN:

170178

AF XY:

0.000153

show subpopulations

Gnomad AFR exome

AF:

0.000255

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:

0.000213

Gnomad OTH exome

AF:

0.000236

GnomAD4 exome

AF:

0.000232

AC:

254

AN:

1094309

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

360537

show subpopulations

African (AFR)

AF:

0.0000760

AC:

AN:

26333

American (AMR)

AF:

0.00

AC:

AN:

34941

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19332

East Asian (EAS)

AF:

0.00

AC:

AN:

30067

South Asian (SAS)

AF:

0.0000187

AC:

AN:

53575

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3974

European-Non Finnish (NFE)

AF:

0.000294

AC:

247

AN:

840855

Other (OTH)

AF:

0.0000872

AC:

AN:

45882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000197

AC:

AN:

111873

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34051

show subpopulations

African (AFR)

AF:

0.0000974

AC:

AN:

30795

American (AMR)

AF:

0.00

AC:

AN:

10615

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3549

South Asian (SAS)

AF:

0.00

AC:

AN:

2680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000358

AC:

AN:

53046

Other (OTH)

AF:

0.00

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000447

AC:

ExAC

AF:

0.0000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.1

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.094

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.83

M_CAP

Benign

0.0088

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.19

PrimateAI

Benign

0.26

PROVEAN

Benign

0.0

REVEL

Benign

0.070

Sift

Benign

0.31

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.21

MVP

0.53

MPC

0.70

ClinPred

0.0046

GERP RS

-2.7

Varity_R

0.057

gMVP

0.51

Mutation Taster

=97/3

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over