rs3747333

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_181332.3(NLGN4X):c.1777C>T(p.Leu593Phe) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1039 hom., 1870 hem., cov: 20)

Exomes 𝑓: 0.057 ( 4236 hom. 27558 hem. )

Failed GnomAD Quality Control

Consequence

NLGN4X
NM_181332.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 4.68

Variant links:

Genes affected

NLGN4X (HGNC:14287): (neuroligin 4 X-linked) This gene encodes a member of the type-B carboxylesterase/lipase protein family. The encoded protein belongs to 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. The encoded protein interacts with discs large homolog 4 (DLG4). Mutations in this gene have been associated with autism and Asperger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

NLGN4X links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014665186).

BP6

Variant X-5893491-G-A is Benign according to our data. Variant chrX-5893491-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 95980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-5893491-G-A is described in Lovd as [Benign]. Variant chrX-5893491-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4X	NM_181332.3 link	c.1777C>T	p.Leu593Phe	missense_variant	Exon 6 of 6	ENST00000381095.8	NP_851849.1	Q8N0W4-1A0A024RBV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8 link	c.1777C>T	p.Leu593Phe	missense_variant	Exon 6 of 6	1	NM_181332.3	ENSP00000370485.3		Q8N0W4-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

12980

AN:

107029

Hom.:

1037

Cov.:

AF XY:

0.0606

AC XY:

1854

AN XY:

30581

FAILED QC

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.0650

Gnomad ASJ

AF:

0.0693

Gnomad EAS

AF:

0.0940

Gnomad SAS

AF:

0.0550

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0949

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.00756

AC:

1311

AN:

173453

Hom.:

233

AF XY:

0.0138

AC XY:

842

AN XY:

61087

show subpopulations

Gnomad AFR exome

AF:

0.0363

Gnomad AMR exome

AF:

0.00372

Gnomad ASJ exome

AF:

0.00292

Gnomad EAS exome

AF:

0.0125

Gnomad SAS exome

AF:

0.00623

Gnomad FIN exome

AF:

0.000916

Gnomad NFE exome

AF:

0.00579

Gnomad OTH exome

AF:

0.00769

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0571

AC:

58041

AN:

1016946

Hom.:

4236

Cov.:

AF XY:

0.0788

AC XY:

27558

AN XY:

349640

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0319

Gnomad4 ASJ exome

AF:

0.0602

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.0641

Gnomad4 FIN exome

AF:

0.0802

Gnomad4 NFE exome

AF:

0.0505

Gnomad4 OTH exome

AF:

0.0727

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.121

AC:

13000

AN:

107064

Hom.:

1039

Cov.:

AF XY:

0.0611

AC XY:

1870

AN XY:

30628

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.0649

Gnomad4 ASJ

AF:

0.0693

Gnomad4 EAS

AF:

0.0949

Gnomad4 SAS

AF:

0.0540

Gnomad4 FIN

AF:

0.0603

Gnomad4 NFE

AF:

0.0949

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.118

Hom.:

888

Bravo

AF:

0.158

ExAC

AF:

0.00102

AC:

118

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 16, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:4

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 28, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Inborn genetic diseases

Benign:1

Dec 13, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Autism, susceptibility to, X-linked 2

Benign:1

May 28, 2019

Mendelics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;T;T;.;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

1.0

.;D;.;D;.

MetaRNN

Benign

0.015

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.9

M;M;M;.;M

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.7

D;.;D;.;D

REVEL

Uncertain

0.38

Sift

Benign

0.052

T;.;T;.;T

Sift4G

Benign

0.077

T;T;T;.;T

Polyphen

0.99

D;D;D;D;D

Vest4

0.56

MVP

0.95

MPC

2.2

ClinPred

0.020

GERP RS

3.2

Varity_R

0.37

gMVP

0.86

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over