chr3-173604893-G-C
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
NM_001365925.2 missense
Scores
1
5
10
Clinical Significance
Conservation
PhyloP100: 9.60
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, NLGN1
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 | 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 | c.295G>C | p.Glu99Gln | missense_variant | 2/7 | NM_001365925.2 | A1 | ||
NLGN1 | ENST00000415045.2 | c.295G>C | p.Glu99Gln | missense_variant | 2/8 | 1 | |||
NLGN1 | ENST00000361589.8 | c.295G>C | p.Glu99Gln | missense_variant | 2/6 | 1 | P2 | ||
NLGN1 | ENST00000457714.5 | c.295G>C | p.Glu99Gln | missense_variant | 3/7 | 1 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250926Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135618
GnomAD3 exomes
AF:
AC:
5
AN:
250926
Hom.:
AF XY:
AC XY:
2
AN XY:
135618
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461524Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727076
GnomAD4 exome
AF:
AC:
15
AN:
1461524
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
727076
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Alfa
AF:
Hom.:
ExAC
?
AF:
AC:
2
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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;.
Vest4
MutPred
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
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at