dbSNP rs6638575: NLGN4X:c.1602-934T>C (chrX-5894600-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181332.3(NLGN4X):c.1602-934T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 18481 hom., 22357 hem., cov: 22)

Failed GnomAD Quality Control

Consequence

NLGN4X
NM_181332.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.754

Publications

2 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

NLGN4X links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_181332.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181332.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NLGN4X	NM_181332.3	MANE Select	c.1602-934T>C	intron	N/A	NP_851849.1	Q8N0W4-1
NLGN4X	NM_001282145.2		c.1602-934T>C	intron	N/A	NP_001269074.1	Q8N0W4-1
NLGN4X	NM_001282146.2		c.1602-934T>C	intron	N/A	NP_001269075.1	Q8N0W4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NLGN4X	ENST00000381095.8	TSL:1 MANE Select	c.1602-934T>C	intron	N/A	ENSP00000370485.3	Q8N0W4-1
NLGN4X	ENST00000538097.6	TSL:1	c.1662-934T>C	intron	N/A	ENSP00000439203.3	Q8N0W4-2
NLGN4X	ENST00000275857.10	TSL:1	c.1602-934T>C	intron	N/A	ENSP00000275857.6	Q8N0W4-1

Frequencies

GnomAD3 genomes

AF:

0.688

AC:

75801

AN:

110111

Hom.:

18486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.624

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.740

Gnomad EAS

AF:

0.784

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.728

Gnomad MID

AF:

0.781

Gnomad NFE

AF:

0.719

Gnomad OTH

AF:

0.670

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.688

AC:

75830

AN:

110164

Hom.:

18481

Cov.:

AF XY:

0.689

AC XY:

22357

AN XY:

32438

show subpopulations

African (AFR)

AF:

0.624

AC:

18879

AN:

30264

American (AMR)

AF:

0.652

AC:

6747

AN:

10341

Ashkenazi Jewish (ASJ)

AF:

0.740

AC:

1943

AN:

2627

East Asian (EAS)

AF:

0.784

AC:

2703

AN:

3446

South Asian (SAS)

AF:

0.714

AC:

1828

AN:

2561

European-Finnish (FIN)

AF:

0.728

AC:

4191

AN:

5757

Middle Eastern (MID)

AF:

0.787

AC:

166

AN:

211

European-Non Finnish (NFE)

AF:

0.719

AC:

37975

AN:

52801

Other (OTH)

AF:

0.668

AC:

992

AN:

1485

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

851

1702

2553

3404

4255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.704

Hom.:

48004

Bravo

AF:

0.680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.74

(source)

DANN

Benign

0.50

PhyloP100

-0.75

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over