rs10127395

Positions:

• chrX-71158679-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN3	NM_181303.2	c.727+3316T>G		intron_variant		ENST00000358741.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN3	ENST00000358741.4	c.727+3316T>G		intron_variant		5	NM_181303.2	A1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 57515 AN: 108613 Hom.: 12681 Cov.: 21 AF XY: 0.519 AC XY: 16100 AN XY: 31027

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

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.546

Alfa AF: 0.466 Hom.: 4372

Bravo AF: 0.555

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

LitVar

Other links and lift over

dbSNP: rs10127395; hg19: chrX-70378529;