3-173604651-C-A

Variant names:

• chr3-173604651-C-A
• NM_001365925.2:c.53C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

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]

ACMG classification

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
NLGN1	NM_001365925.2	c.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
NLGN1	ENST00000695368.1	c.53C>A	p.Ala18Glu	missense_variant	Exon 2 of 7		NM_001365925.2	ENSP00000511841.1

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

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;