Variant 3-173604807-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_001365925.2(NLGN1):c.209A>G(p.Asn70Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000713 in 1,613,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N70D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

NLGN1
NM_001365925.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

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 Likely_benign. Variant got -1 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), NLGN1. . Gene score misZ 2.2182 (greater than the threshold 3.09). Trascript score misZ 3.3825 (greater than threshold 3.09). GenCC has associacion of gene with autism, susceptibility to, 20.

BP4

Computational evidence support a benign effect (MetaRNN=0.23145923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2 linkuse as main transcript	c.209A>G	p.Asn70Ser	missense_variant	2/7	ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1 linkuse as main transcript	c.209A>G	p.Asn70Ser	missense_variant	2/7		NM_001365925.2	A1
NLGN1	ENST00000415045.2 linkuse as main transcript	c.209A>G	p.Asn70Ser	missense_variant	2/8	1			Q8N2Q7-3
NLGN1	ENST00000361589.8 linkuse as main transcript	c.209A>G	p.Asn70Ser	missense_variant	2/6	1		P2	Q8N2Q7-2
NLGN1	ENST00000457714.5 linkuse as main transcript	c.209A>G	p.Asn70Ser	missense_variant	3/7	1		P2	Q8N2Q7-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250716

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000759

AC:

111

AN:

1461546

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000863

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.209A>G (p.N70S) alteration is located in exon 3 (coding exon 1) of the NLGN1 gene. This alteration results from a A to G substitution at nucleotide position 209, causing the asparagine (N) at amino acid position 70 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

.;.;T

Eigen

Benign

-0.041

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-0.34

N;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.61

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.67

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.37

MutPred

0.40

Gain of disorder (P = 0.1216);Gain of disorder (P = 0.1216);Gain of disorder (P = 0.1216);

MVP

0.56

MPC

0.78

ClinPred

0.21

GERP RS

5.6

gMVP

0.23

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