chr3-173604819-T-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_001365925.2(NLGN1):c.221T>G(p.Leu74Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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
NM_001365925.2 missense
Scores
9
5
2
Clinical Significance
Conservation
PhyloP100: 7.67
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 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, NLGN1
PP3
MetaRNN computational evidence supports a deleterious effect, 0.857
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLGN1 | NM_001365925.2 | c.221T>G | p.Leu74Trp | missense_variant | 2/7 | ENST00000695368.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLGN1 | ENST00000695368.1 | c.221T>G | p.Leu74Trp | missense_variant | 2/7 | NM_001365925.2 | A1 | ||
NLGN1 | ENST00000415045.2 | c.221T>G | p.Leu74Trp | missense_variant | 2/8 | 1 | |||
NLGN1 | ENST00000361589.8 | c.221T>G | p.Leu74Trp | missense_variant | 2/6 | 1 | P2 | ||
NLGN1 | ENST00000457714.5 | c.221T>G | p.Leu74Trp | missense_variant | 3/7 | 1 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome 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
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 13, 2022 | The c.221T>G (p.L74W) alteration is located in exon 3 (coding exon 1) of the NLGN1 gene. This alteration results from a T to G substitution at nucleotide position 221, causing the leucine (L) at amino acid position 74 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Benign
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Loss of solvent accessibility (P = 0.0352);Loss of solvent accessibility (P = 0.0352);Loss of solvent accessibility (P = 0.0352);
MVP
MPC
ClinPred
D
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
Publications
No publications associated with this variant yet.