X-71152405-T-C

Variant names:

• chrX-71152405-T-C
• rs5981079
• NM_181303.2:c.518-1072T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN3	NM_181303.2	MANE Select	c.518-1072T>C		intron	N/A	NP_851820.1
	NLGN3	NM_018977.4		c.458-1072T>C		intron	N/A	NP_061850.2
	NLGN3	NM_001166660.2		c.458-2809T>C		intron	N/A	NP_001160132.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN3	ENST00000358741.4	TSL:5 MANE Select	c.518-1072T>C		intron	N/A	ENSP00000351591.4
	NLGN3	ENST00000374051.7	TSL:1	c.458-1072T>C		intron	N/A	ENSP00000363163.3
	NLGN3	ENST00000395855.7	TSL:1	c.458-2809T>C		intron	N/A	ENSP00000379196.3

Frequencies

GnomAD3 genomes AF: 0.530 AC: 57302 AN: 108177 Hom.: 12395 Cov.: 21

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

African (AFR) AF: 0.789 AC: 23224 AN: 29430

American (AMR) AF: 0.567 AC: 5742 AN: 10124

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1375 AN: 2597

East Asian (EAS) AF: 0.353 AC: 1204 AN: 3411

South Asian (SAS) AF: 0.434 AC: 1061 AN: 2442

European-Finnish (FIN) AF: 0.354 AC: 2025 AN: 5713

Middle Eastern (MID) AF: 0.567 AC: 119 AN: 210

European-Non Finnish (NFE) AF: 0.413 AC: 21562 AN: 52194

Other (OTH) AF: 0.543 AC: 786 AN: 1448

Alfa AF: 0.443 Hom.: 28348

Bravo AF: 0.560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.70
DANN	Benign	0.60
PhyloP100		-2.3
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: rs5981079; hg19: chrX-70372255;