NM_181303.2:c.517+1489G>A

Variant names:

• chrX-71150394-G-A
• rs4844285
• NM_181303.2:c.517+1489G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181303.2(NLGN3):​c.517+1489G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (14085 hom., 18045 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: NLGN3 NM_181303.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 10 publications found

Genes affected

NLGN3 (HGNC:14289): (neuroligin 3) 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. Mutations in this gene may be associated with autism and Asperger syndrome. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Oct 2009]

NLGN3 Gene-Disease associations (from GenCC):

• autism, susceptibility to, X-linked 1

  Inheritance: Unknown, XL Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: MODERATE Submitted by: Illumina, ClinGen

ENSG00000228427 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN3	NM_181303.2	c.517+1489G>A		intron_variant	Intron 3 of 7	ENST00000358741.4	NP_851820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN3	ENST00000358741.4	c.517+1489G>A		intron_variant	Intron 3 of 7	5	NM_181303.2	ENSP00000351591.4
NLGN3	ENST00000685718.1	n.457+2188G>A		intron_variant	Intron 2 of 7			ENSP00000510514.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 62917 AN: 110237 Hom.: 14082 Cov.: 22

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.593

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.571 AC: 62976 AN: 110291 Hom.: 14085 Cov.: 22 AF XY: 0.554 AC XY: 18045 AN XY: 32545

African (AFR) AF: 0.824 AC: 24930 AN: 30268

American (AMR) AF: 0.608 AC: 6294 AN: 10358

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 1524 AN: 2624

East Asian (EAS) AF: 0.308 AC: 1075 AN: 3491

South Asian (SAS) AF: 0.461 AC: 1223 AN: 2653

European-Finnish (FIN) AF: 0.391 AC: 2256 AN: 5772

Middle Eastern (MID) AF: 0.659 AC: 139 AN: 211

European-Non Finnish (NFE) AF: 0.462 AC: 24351 AN: 52736

Other (OTH) AF: 0.600 AC: 904 AN: 1506

Alfa AF: 0.515 Hom.: 49581

Bravo AF: 0.596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.68
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4844285; hg19: chrX-70370244;