rs10127395

Variant names:

• chrX-71158679-T-G
• rs10127395
• NM_181303.2:c.727+3316T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181303.2(NLGN3):​c.727+3316T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 108,664 control chromosomes in the GnomAD database, including 12,677 homozygotes. There are 16,159 hemizygotes in GnomAD. 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 0.53 (12677 hom., 16159 hem., cov: 21)
• Consequence: NLGN3 NM_181303.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 3 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: XL, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• X-linked complex neurodevelopmental disorder

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

ENSG00000228427 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181303.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN3	NM_181303.2	MANE Select	c.727+3316T>G		intron	N/A	NP_851820.1	X5DNV3
	NLGN3	NM_018977.4		c.667+3316T>G		intron	N/A	NP_061850.2	Q9NZ94-2
	NLGN3	NM_001166660.2		c.607+3316T>G		intron	N/A	NP_001160132.1	X5D7L6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN3	ENST00000358741.4	TSL:5 MANE Select	c.727+3316T>G		intron	N/A	ENSP00000351591.4	Q9NZ94-1
	NLGN3	ENST00000374051.7	TSL:1	c.667+3316T>G		intron	N/A	ENSP00000363163.3	Q9NZ94-2
	NLGN3	ENST00000395855.7	TSL:1	c.607+3316T>G		intron	N/A	ENSP00000379196.3	E7EVK0

Frequencies

GnomAD3 genomes AF: 0.530 AC: 57515 AN: 108613 Hom.: 12681 Cov.: 21

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.530 AC: 57569 AN: 108664 Hom.: 12677 Cov.: 21 AF XY: 0.520 AC XY: 16159 AN XY: 31088

African (AFR) AF: 0.836 AC: 25088 AN: 30001

American (AMR) AF: 0.573 AC: 5861 AN: 10224

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 1523 AN: 2597

East Asian (EAS) AF: 0.181 AC: 608 AN: 3360

South Asian (SAS) AF: 0.253 AC: 640 AN: 2533

European-Finnish (FIN) AF: 0.391 AC: 2166 AN: 5542

Middle Eastern (MID) AF: 0.625 AC: 130 AN: 208

European-Non Finnish (NFE) AF: 0.393 AC: 20482 AN: 52051

Other (OTH) AF: 0.546 AC: 812 AN: 1488

Alfa AF: 0.466 Hom.: 4372

Bravo AF: 0.555

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.15
DANN	Benign	0.81
PhyloP100		-0.31
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10127395;

hg19: chrX-70378529;