rs1882409

Variant names:

• chrX-6215771-G-A
• rs1882409
• NM_181332.3:c.-306+12770C>T

Variant summary

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

The NM_181332.3(NLGN4X):​c.-306+12770C>T 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 0.65 (17171 hom., 20907 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 4 publications found

Genes affected

NLGN4X (HGNC:14287): (neuroligin 4 X-linked) This gene encodes a member of the type-B carboxylesterase/lipase protein family. The encoded protein belongs to 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. The encoded protein interacts with discs large homolog 4 (DLG4). Mutations in this gene have been associated with autism and Asperger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

NLGN4X Gene-Disease associations (from GenCC):

• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• autism, susceptibility to, X-linked 2

  Inheritance: XL Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181332.3. 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
	NLGN4X	NM_181332.3	MANE Select	c.-306+12770C>T		intron	N/A	NP_851849.1	Q8N0W4-1
	NLGN4X	NM_001282145.2		c.-613+12770C>T		intron	N/A	NP_001269074.1	Q8N0W4-1
	NLGN4X	NM_001282146.2		c.-306+11109C>T		intron	N/A	NP_001269075.1	Q8N0W4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4X	ENST00000381095.8	TSL:1 MANE Select	c.-306+12770C>T		intron	N/A	ENSP00000370485.3	Q8N0W4-1
	NLGN4X	ENST00000275857.10	TSL:1	c.-306+11918C>T		intron	N/A	ENSP00000275857.6	Q8N0W4-1
	NLGN4X	ENST00000381092.1	TSL:2	c.-613+12770C>T		intron	N/A	ENSP00000370482.1	Q8N0W4-1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 71440 AN: 110056 Hom.: 17162 Cov.: 22

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.615

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: 0.649 AC: 71507 AN: 110114 Hom.: 17171 Cov.: 22 AF XY: 0.646 AC XY: 20907 AN XY: 32356

African (AFR) AF: 0.820 AC: 24832 AN: 30281

American (AMR) AF: 0.641 AC: 6638 AN: 10348

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1392 AN: 2632

East Asian (EAS) AF: 0.294 AC: 1019 AN: 3469

South Asian (SAS) AF: 0.558 AC: 1449 AN: 2595

European-Finnish (FIN) AF: 0.681 AC: 3864 AN: 5678

Middle Eastern (MID) AF: 0.583 AC: 123 AN: 211

European-Non Finnish (NFE) AF: 0.584 AC: 30770 AN: 52722

Other (OTH) AF: 0.614 AC: 921 AN: 1500

Alfa AF: 0.608 Hom.: 87059

Bravo AF: 0.657

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.44
PhyloP100		-0.50
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: rs1882409;

hg19: chrX-6133812;