chrX-71147759-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_181303.2(NLGN3):c.10C>T(p.Arg4Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,203,792 control chromosomes in the GnomAD database, including 2 homozygotes. There are 154 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.00032 ( 2 hom. 149 hem. )

Consequence

NLGN3
NM_181303.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.547

Publications

2 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065551996).

BP6

Variant X-71147759-C-T is Benign according to our data. Variant chrX-71147759-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 425503.

BS2

High Hemizygotes in GnomAd4 at 5 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.10C>T	p.Arg4Trp	missense	Exon 2 of 8	NP_851820.1	X5DNV3
NLGN3	NM_018977.4		c.10C>T	p.Arg4Trp	missense	Exon 2 of 7	NP_061850.2	Q9NZ94-2
NLGN3	NM_001166660.2		c.10C>T	p.Arg4Trp	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.10C>T	p.Arg4Trp	missense	Exon 2 of 8	ENSP00000351591.4	Q9NZ94-1
NLGN3	ENST00000374051.7	TSL:1	c.10C>T	p.Arg4Trp	missense	Exon 2 of 7	ENSP00000363163.3	Q9NZ94-2
NLGN3	ENST00000395855.7	TSL:1	c.10C>T	p.Arg4Trp	missense	Exon 2 of 5	ENSP00000379196.3	E7EVK0

Frequencies

GnomAD3 genomes

AF:

0.000161

AC:

AN:

111878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00444

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000718

AC:

120

AN:

167141

AF XY:

0.000806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000681

Gnomad OTH exome

AF:

0.000480

GnomAD4 exome

AF:

0.000323

AC:

353

AN:

1091862

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

149

AN XY:

358604

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26302

American (AMR)

AF:

0.0000862

AC:

AN:

34797

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19301

East Asian (EAS)

AF:

0.00

AC:

AN:

29994

South Asian (SAS)

AF:

0.00461

AC:

246

AN:

53330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38760

Middle Eastern (MID)

AF:

0.00233

AC:

AN:

3869

European-Non Finnish (NFE)

AF:

0.0000762

AC:

AN:

839714

Other (OTH)

AF:

0.000677

AC:

AN:

45795

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

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

<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:

0.000152

AC:

AN:

111930

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

34114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30821

American (AMR)

AF:

0.00

AC:

AN:

10631

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3561

South Asian (SAS)

AF:

0.00408

AC:

AN:

2694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6119

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53045

Other (OTH)

AF:

0.00

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.0000868

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000152

AC:

ExAC

AF:

0.000772

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Cone-rod dystrophy (1)

Inborn genetic diseases (1)

Intellectual disability (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.10

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

0.55

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.23

REVEL

Benign

0.19

Sift

Benign

0.19

Sift4G

Uncertain

0.023

Polyphen

0.0020

Vest4

0.21

MVP

0.74

MPC

0.76

ClinPred

0.052

GERP RS

1.6

Varity_R

0.076

gMVP

0.59

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over