Variant 3-173604893-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4

The NM_001365925.2(NLGN1):c.295G>C(p.Glu99Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

NLGN1
NM_001365925.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 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=0.2695191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2 linkuse as main transcript	c.295G>C	p.Glu99Gln	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.295G>C	p.Glu99Gln	missense_variant	2/7		NM_001365925.2	A1
NLGN1	ENST00000415045.2 linkuse as main transcript	c.295G>C	p.Glu99Gln	missense_variant	2/8	1			Q8N2Q7-3
NLGN1	ENST00000361589.8 linkuse as main transcript	c.295G>C	p.Glu99Gln	missense_variant	2/6	1		P2	Q8N2Q7-2
NLGN1	ENST00000457714.5 linkuse as main transcript	c.295G>C	p.Glu99Gln	missense_variant	3/7	1		P2	Q8N2Q7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250926

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461524

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.000556

Hom.:

ExAC

AF:

0.0000165

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

Jun 02, 2023

The c.295G>C (p.E99Q) alteration is located in exon 3 (coding exon 1) of the NLGN1 gene. This alteration results from a G to C substitution at nucleotide position 295, causing the glutamic acid (E) at amino acid position 99 to be replaced by a glutamine (Q). 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

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.33

.;.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-0.58

N;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.6

N;N;D

REVEL

Benign

0.26

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.62

P;P;.

Vest4

0.63

MutPred

0.40

Loss of glycosylation at P100 (P = 0.0072);Loss of glycosylation at P100 (P = 0.0072);Loss of glycosylation at P100 (P = 0.0072);

MVP

0.54

MPC

1.1

ClinPred

0.35

GERP RS

5.6

gMVP

0.57

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