X-71152405-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181303.2(NLGN3):c.518-1072T>C 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 108,233 control chromosomes in the GnomAD database, including 12,397 homozygotes. There are 15,476 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 (12397 hom., 15476 hem., cov: 21)
• Consequence: NLGN3 NM_181303.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN3	NM_181303.2	c.518-1072T>C		intron_variant		ENST00000358741.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN3	ENST00000358741.4	c.518-1072T>C		intron_variant		5	NM_181303.2	A1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 57302 AN: 108177 Hom.: 12395 Cov.: 21 AF XY: 0.504 AC XY: 15417 AN XY: 30573

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.530 AC: 57361 AN: 108233 Hom.: 12397 Cov.: 21 AF XY: 0.505 AC XY: 15476 AN XY: 30639

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.543

Alfa AF: 0.436 Hom.: 22700

Bravo AF: 0.560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.70
Dann	Benign	0.60

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: rs5981079; hg19: chrX-70372255;