Variant X-5892533-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181332.3(NLGN4X):c.*284G>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 0.381 in 331,094 control chromosomes in the GnomAD database, including 18,698 homozygotes. There are 38,258 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 4931 hom., 10746 hem., cov: 23)

Exomes 𝑓: 0.41 ( 13767 hom. 27512 hem. )

Consequence

NLGN4X
NM_181332.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00700

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant X-5892533-C-T is Benign according to our data. Variant chrX-5892533-C-T is described in ClinVar as [Benign]. Clinvar id is 1251892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLGN4X	NM_181332.3 linkuse as main transcript	c.*284G>A		3_prime_UTR_variant	6/6	ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8 linkuse as main transcript	c.*284G>A		3_prime_UTR_variant	6/6	1	NM_181332.3	ENSP00000370485	P4	Q8N0W4-1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

35416

AN:

110912

Hom.:

4932

Cov.:

AF XY:

0.324

AC XY:

10745

AN XY:

33150

show subpopulations

Gnomad AFR

AF:

0.0739

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.445

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.324

GnomAD4 exome

AF:

0.412

AC:

90738

AN:

220126

Hom.:

13767

Cov.:

AF XY:

0.419

AC XY:

27512

AN XY:

65596

show subpopulations

Gnomad4 AFR exome

AF:

0.0747

Gnomad4 AMR exome

AF:

0.362

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.616

Gnomad4 SAS exome

AF:

0.441

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.389

GnomAD4 genome

AF:

0.319

AC:

35410

AN:

110968

Hom.:

4931

Cov.:

AF XY:

0.324

AC XY:

10746

AN XY:

33216

show subpopulations

Gnomad4 AFR

AF:

0.0738

Gnomad4 AMR

AF:

0.339

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.619

Gnomad4 SAS

AF:

0.445

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.411

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.401

Hom.:

36479

Bravo

AF:

0.303

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.23

DANN

Benign

0.51

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