rs7049300

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_181332.3(NLGN4X):c.933C>T(p.Thr311=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,209,508 control chromosomes in the GnomAD database, including 6,131 homozygotes. There are 46,435 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 751 hom., 4089 hem., cov: 22)

Exomes 𝑓: 0.12 ( 5380 hom. 42346 hem. )

Consequence

NLGN4X
NM_181332.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.375

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=-0.63).

BP6

Variant X-5903745-G-A is Benign according to our data. Variant chrX-5903745-G-A is described in ClinVar as [Benign]. Clinvar id is 95987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-5903745-G-A is described in Lovd as [Likely_benign]. Variant chrX-5903745-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.375 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 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.933C>T	p.Thr311=	synonymous_variant	5/6	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.933C>T	p.Thr311=	synonymous_variant	5/6	1	NM_181332.3	ENSP00000370485	P4	Q8N0W4-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

14341

AN:

111235

Hom.:

751

Cov.:

AF XY:

0.122

AC XY:

4074

AN XY:

33463

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.0824

Gnomad ASJ

AF:

0.0852

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.0909

Gnomad FIN

AF:

0.0983

Gnomad MID

AF:

0.119

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.108

AC:

19778

AN:

183403

Hom.:

794

AF XY:

0.110

AC XY:

7440

AN XY:

67837

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.0416

Gnomad ASJ exome

AF:

0.0920

Gnomad EAS exome

AF:

0.107

Gnomad SAS exome

AF:

0.0874

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.118

AC:

129368

AN:

1098219

Hom.:

5380

Cov.:

AF XY:

0.116

AC XY:

42346

AN XY:

363575

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.0464

Gnomad4 ASJ exome

AF:

0.0904

Gnomad4 EAS exome

AF:

0.122

Gnomad4 SAS exome

AF:

0.0883

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.129

AC:

14357

AN:

111289

Hom.:

751

Cov.:

AF XY:

0.122

AC XY:

4089

AN XY:

33527

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.0822

Gnomad4 ASJ

AF:

0.0852

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.0900

Gnomad4 FIN

AF:

0.0983

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.114

Hom.:

924

Bravo

AF:

0.132

EpiCase

AF:

0.125

EpiControl

AF:

0.128

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 16, 2013	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2015

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. -

not provided

Benign:1

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

-0.63

CADD

Benign

1.3

DANN

Benign

0.70

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