NM_181303.2:c.518-1753T>G

Variant names:

• chrX-71151724-T-G
• rs4844286
• NM_181303.2:c.518-1753T>G

Variant summary

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

The NM_181303.2(NLGN3):​c.518-1753T>G 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 0.51 (10350 hom., 16467 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: NLGN3 NM_181303.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 5 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

LOC124905197 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN3	NM_181303.2	c.518-1753T>G		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.518-1753T>G		intron_variant	Intron 3 of 7	5	NM_181303.2	ENSP00000351591.4
NLGN3	ENST00000685718.1	n.458-1753T>G		intron_variant	Intron 2 of 7			ENSP00000510514.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 56205 AN: 110999 Hom.: 10353 Cov.: 23

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.555

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: 0.506 AC: 56238 AN: 111053 Hom.: 10350 Cov.: 23 AF XY: 0.495 AC XY: 16467 AN XY: 33265

African (AFR) AF: 0.570 AC: 17394 AN: 30538

American (AMR) AF: 0.588 AC: 6179 AN: 10514

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1493 AN: 2639

East Asian (EAS) AF: 0.285 AC: 995 AN: 3491

South Asian (SAS) AF: 0.417 AC: 1106 AN: 2652

European-Finnish (FIN) AF: 0.423 AC: 2518 AN: 5949

Middle Eastern (MID) AF: 0.631 AC: 135 AN: 214

European-Non Finnish (NFE) AF: 0.478 AC: 25268 AN: 52858

Other (OTH) AF: 0.563 AC: 859 AN: 1525

Alfa AF: 0.412 Hom.: 3657

Bravo AF: 0.522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0080
DANN	Benign	0.42
PhyloP100		-2.7
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: rs4844286; hg19: chrX-70371574;