X-5892997-C-T

Position:

chrX-5892997-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_181332.3(NLGN4X):c.2271G>A(p.Pro757=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,209,095 control chromosomes in the GnomAD database, including 13 homozygotes. There are 383 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 6 hom., 174 hem., cov: 21)

Exomes 𝑓: 0.00062 ( 7 hom. 209 hem. )

Consequence

NLGN4X
NM_181332.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -7.76

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-5892997-C-T is Benign according to our data. Variant chrX-5892997-C-T is described in ClinVar as [Benign]. Clinvar id is 95982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.76 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00569 (631/110832) while in subpopulation AFR AF= 0.02 (608/30440). AF 95% confidence interval is 0.0187. There are 6 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLGN4X	NM_181332.3 linkuse as main transcript	c.2271G>A	p.Pro757=	synonymous_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.2271G>A	p.Pro757=	synonymous_variant	6/6	1	NM_181332.3	ENSP00000370485	P4	Q8N0W4-1

Frequencies

GnomAD3 genomes

AF:

0.00567

AC:

628

AN:

110778

Hom.:

Cov.:

AF XY:

0.00521

AC XY:

172

AN XY:

33038

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000394

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00471

GnomAD3 exomes

AF:

0.00168

AC:

309

AN:

183514

Hom.:

AF XY:

0.00116

AC XY:

AN XY:

67944

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.000547

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000488

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000620

AC:

681

AN:

1098263

Hom.:

Cov.:

AF XY:

0.000575

AC XY:

209

AN XY:

363617

show subpopulations

Gnomad4 AFR exome

AF:

0.0206

Gnomad4 AMR exome

AF:

0.000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000701

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00569

AC:

631

AN:

110832

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

174

AN XY:

33102

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000396

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00465

Alfa

AF:

0.000871

Hom.:

Bravo

AF:

0.00685

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 29, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 19, 2013	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 03, 2016

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.068

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