rs1751121113

Variant names:

• chr3-173604857-G-A
• NM_001365925.2:c.259G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-173604857-G-A
• chr3-173604857-G-T

Variant summary

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

The NM_001365925.2(NLGN1):​c.259G>A​(p.Ala87Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A87S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NLGN1 NM_001365925.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.46

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=0.3243196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.259G>A	p.Ala87Thr	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.259G>A	p.Ala87Thr	missense_variant	Exon 2 of 7		NM_001365925.2	ENSP00000511841.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461532 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727068

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.14	.;.;T
Eigen	Benign	0.049
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.4	L;L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.79	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.53	T;T;T
Sift4G	Benign	0.46	T;T;T
Polyphen		0.20	B;B;.
Vest4		0.50
MutPred		0.57		Gain of glycosylation at Y85 (P = 0.0131);Gain of glycosylation at Y85 (P = 0.0131);Gain of glycosylation at Y85 (P = 0.0131);
MVP		0.56
MPC		0.59
ClinPred		0.80	D
GERP RS		5.6
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr3-173322647;