X-5892907-C-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_181332.3(NLGN4X):​c.2361G>A​(p.Thr787Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000091 in 1,209,077 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.0000091 ( 0 hom. 6 hem. )

Consequence

NLGN4X
NM_181332.3 synonymous

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0940

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • X-linked complex neurodevelopmental disorder
    Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
  • autism, susceptibility to, X-linked 2
    Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP7
Synonymous conserved (PhyloP=0.094 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 6 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NLGN4XNM_181332.3 linkc.2361G>A p.Thr787Thr synonymous_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
NLGN4XENST00000381095.8 linkc.2361G>A p.Thr787Thr synonymous_variant Exon 6 of 6 1 NM_181332.3 ENSP00000370485.3 Q8N0W4-1

Frequencies

GnomAD3 genomes
AF:
0.00000902
AC:
1
AN:
110827
Hom.:
0
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.0000329
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000911
AC:
10
AN:
1098250
Hom.:
0
Cov.:
32
AF XY:
0.0000165
AC XY:
6
AN XY:
363604
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26403
American (AMR)
AF:
0.00
AC:
0
AN:
35207
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19386
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30206
South Asian (SAS)
AF:
0.00
AC:
0
AN:
54145
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40534
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4137
European-Non Finnish (NFE)
AF:
0.0000119
AC:
10
AN:
842134
Other (OTH)
AF:
0.00
AC:
0
AN:
46098
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<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:
0.00000902
AC:
1
AN:
110827
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33031
show subpopulations
African (AFR)
AF:
0.0000329
AC:
1
AN:
30419
American (AMR)
AF:
0.00
AC:
0
AN:
10377
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2634
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3494
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2588
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
5919
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
239
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
52985
Other (OTH)
AF:
0.00
AC:
0
AN:
1485
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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.:
0
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 09, 2015
Genetic Services Laboratory, University of Chicago
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
1.1
DANN
Benign
0.56
PhyloP100
0.094

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

Other links and lift over

dbSNP: rs374449420; hg19: chrX-5810948; COSMIC: COSV99323338; API