Variant 3-173800298-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000415045.2(NLGN1):c.559C>T(p.Leu187Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00483 in 1,191,540 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0050 ( 17 hom. )

Consequence

NLGN1
ENST00000415045.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.76

Variant links:

Genes affected

NLGN1 (HGNC:14291): (neuroligin 1) This gene encodes a member of 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. [provided by RefSeq, Jul 2008]

NLGN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008828968).

BP6

Variant 3-173800298-C-T is Benign according to our data. Variant chr3-173800298-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3037839.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2 linkuse as main transcript	c.554-7382C>T		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000415045.2 linkuse as main transcript	c.559C>T	p.Leu187Phe	missense_variant	4/8	1			Q8N2Q7-3
NLGN1	ENST00000695368.1 linkuse as main transcript	c.554-7382C>T		intron_variant			NM_001365925.2	A1
NLGN1	ENST00000361589.8 linkuse as main transcript	c.494-7382C>T		intron_variant		1		P2	Q8N2Q7-2
NLGN1	ENST00000457714.5 linkuse as main transcript	c.494-7382C>T		intron_variant		1		P2	Q8N2Q7-2

Frequencies

GnomAD3 genomes

AF:

0.00402

AC:

605

AN:

150474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00788

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00531

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00544

Gnomad OTH

AF:

0.00484

GnomAD3 exomes

AF:

0.00283

AC:

290

AN:

102434

Hom.:

AF XY:

0.00290

AC XY:

165

AN XY:

56824

show subpopulations

Gnomad AFR exome

AF:

0.00115

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.000399

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000573

Gnomad FIN exome

AF:

0.00511

Gnomad NFE exome

AF:

0.00419

Gnomad OTH exome

AF:

0.00570

GnomAD4 exome

AF:

0.00495

AC:

5154

AN:

1040946

Hom.:

Cov.:

AF XY:

0.00464

AC XY:

2364

AN XY:

510006

show subpopulations

Gnomad4 AFR exome

AF:

0.000430

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.0000715

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000485

Gnomad4 FIN exome

AF:

0.00459

Gnomad4 NFE exome

AF:

0.00562

Gnomad4 OTH exome

AF:

0.00442

GnomAD4 genome

AF:

0.00401

AC:

604

AN:

150594

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

272

AN XY:

73464

show subpopulations

Gnomad4 AFR

AF:

0.00129

Gnomad4 AMR

AF:

0.00787

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00531

Gnomad4 NFE

AF:

0.00542

Gnomad4 OTH

AF:

0.00479

Alfa

AF:

0.00364

Hom.:

Bravo

AF:

0.00446

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00441

AC:

ExAC

AF:

0.00130

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NLGN1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 04, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

Cadd

Benign

Dann

Benign

0.89

DEOGEN2

Benign

0.12

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.060

FATHMM_MKL

Benign

0.00072

LIST_S2

Benign

0.73

M_CAP

Benign

0.015

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.92

MutationTaster

Benign

0.96

D;D;D;D

PROVEAN

Benign

-0.68

REVEL

Benign

0.28

Sift

Benign

0.72

Sift4G

Benign

0.40

MVP

0.92

ClinPred

0.0068

GERP RS

4.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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