X-5892715-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181332.3(NLGN4X):​c.*102G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,112,611 control chromosomes in the GnomAD database, including 41,117 homozygotes. There are 106,097 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 6558 hom., 11781 hem., cov: 22)
Exomes 𝑓: 0.31 ( 34559 hom. 94316 hem. )

Consequence

NLGN4X
NM_181332.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.452

Publications

8 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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant X-5892715-C-T is Benign according to our data. Variant chrX-5892715-C-T is described in ClinVar as [Benign]. Clinvar id is 1238862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NLGN4XNM_181332.3 linkc.*102G>A 3_prime_UTR_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.*102G>A 3_prime_UTR_variant Exon 6 of 6 1 NM_181332.3 ENSP00000370485.3 Q8N0W4-1

Frequencies

GnomAD3 genomes
AF:
0.378
AC:
41590
AN:
110091
Hom.:
6558
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.604
Gnomad AMI
AF:
0.392
Gnomad AMR
AF:
0.316
Gnomad ASJ
AF:
0.307
Gnomad EAS
AF:
0.142
Gnomad SAS
AF:
0.248
Gnomad FIN
AF:
0.256
Gnomad MID
AF:
0.215
Gnomad NFE
AF:
0.302
Gnomad OTH
AF:
0.343
GnomAD4 exome
AF:
0.308
AC:
309113
AN:
1002466
Hom.:
34559
Cov.:
19
AF XY:
0.311
AC XY:
94316
AN XY:
302982
show subpopulations
African (AFR)
AF:
0.616
AC:
14991
AN:
24338
American (AMR)
AF:
0.280
AC:
8208
AN:
29331
Ashkenazi Jewish (ASJ)
AF:
0.310
AC:
5557
AN:
17954
East Asian (EAS)
AF:
0.145
AC:
4084
AN:
28201
South Asian (SAS)
AF:
0.261
AC:
12532
AN:
48041
European-Finnish (FIN)
AF:
0.276
AC:
9409
AN:
34089
Middle Eastern (MID)
AF:
0.238
AC:
928
AN:
3903
European-Non Finnish (NFE)
AF:
0.310
AC:
240220
AN:
773743
Other (OTH)
AF:
0.308
AC:
13184
AN:
42866
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
7528
15056
22583
30111
37639
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
8364
16728
25092
33456
41820
<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:
0.378
AC:
41630
AN:
110145
Hom.:
6558
Cov.:
22
AF XY:
0.363
AC XY:
11781
AN XY:
32451
show subpopulations
African (AFR)
AF:
0.604
AC:
18177
AN:
30079
American (AMR)
AF:
0.316
AC:
3280
AN:
10384
Ashkenazi Jewish (ASJ)
AF:
0.307
AC:
806
AN:
2627
East Asian (EAS)
AF:
0.143
AC:
497
AN:
3481
South Asian (SAS)
AF:
0.246
AC:
633
AN:
2576
European-Finnish (FIN)
AF:
0.256
AC:
1506
AN:
5880
Middle Eastern (MID)
AF:
0.204
AC:
44
AN:
216
European-Non Finnish (NFE)
AF:
0.302
AC:
15918
AN:
52738
Other (OTH)
AF:
0.339
AC:
505
AN:
1490
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
861
1722
2582
3443
4304
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
398
796
1194
1592
1990
<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:
0.329
Hom.:
2075
Bravo
AF:
0.392

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Jun 19, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
0.077
DANN
Benign
0.52
PhyloP100
-0.45
Mutation Taster
=100/0
polymorphism (auto)

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: rs3810688; hg19: chrX-5810756; COSMIC: COSV52009610; API