3-173604651-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001365925.2(NLGN1):​c.53C>A​(p.Ala18Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NLGN1
NM_001365925.2 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27047157).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NLGN1NM_001365925.2 linkc.53C>A p.Ala18Glu missense_variant Exon 2 of 7 ENST00000695368.1 NP_001352854.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NLGN1ENST00000695368.1 linkc.53C>A p.Ala18Glu missense_variant Exon 2 of 7 NM_001365925.2 ENSP00000511841.1 A0A8Q3SHM6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jul 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.53C>A (p.A18E) alteration is located in exon 3 (coding exon 1) of the NLGN1 gene. This alteration results from a C to A substitution at nucleotide position 53, causing the alanine (A) at amino acid position 18 to be replaced by a glutamic acid (E). 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
0.083
D
BayesDel_noAF
Benign
-0.12
CADD
Benign
15
DANN
Benign
0.92
DEOGEN2
Benign
0.036
.;.;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.69
.;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N;.
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.33
N;N;N
REVEL
Uncertain
0.36
Sift
Uncertain
0.028
D;D;D
Sift4G
Benign
0.95
T;T;T
Polyphen
0.016
B;B;.
Vest4
0.39
MutPred
0.49
Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);
MVP
0.96
MPC
0.42
ClinPred
0.13
T
GERP RS
3.8
gMVP
0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-173322441; COSMIC: COSV64340897; COSMIC: COSV64340897; API