chrX-5890820-G-A

Variant names:

• chrX-5890820-G-A
• rs1882260
• NM_181332.3:c.*1997C>T

Variant summary

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

The NM_181332.3(NLGN4X):​c.*1997C>T variant causes a 3 prime UTR 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 0.70 (19032 hom., 23253 hem., cov: 23)
  • Exomes 𝑓: 0.71 (30879 hom. 53433 hem.)
  • Failed GnomAD Quality Control
• Consequence: NLGN4X NM_181332.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 7 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.*1997C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8	c.*1997C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_181332.3	ENSP00000370485.3
NLGN4X	ENST00000275857.10	c.*1997C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000275857.6
NLGN4X	ENST00000381093.6	c.*1997C>T		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000370483.3
NLGN4X	ENST00000477079.1	n.277+12257C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.700 AC: 77556 AN: 110818 Hom.: 19038 Cov.: 23

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.676

GnomAD4 exome AF: 0.715 AC: 139916 AN: 195707 Hom.: 30879 Cov.: 0 AF XY: 0.723 AC XY: 53433 AN XY: 73887

African (AFR) AF: 0.677 AC: 3984 AN: 5883

American (AMR) AF: 0.660 AC: 11643 AN: 17653

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 4819 AN: 6505

East Asian (EAS) AF: 0.780 AC: 5095 AN: 6535

South Asian (SAS) AF: 0.711 AC: 22114 AN: 31122

European-Finnish (FIN) AF: 0.729 AC: 6205 AN: 8516

Middle Eastern (MID) AF: 0.749 AC: 524 AN: 700

European-Non Finnish (NFE) AF: 0.721 AC: 78771 AN: 109222

Other (OTH) AF: 0.706 AC: 6761 AN: 9571

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.700 AC: 77584 AN: 110870 Hom.: 19032 Cov.: 23 AF XY: 0.703 AC XY: 23253 AN XY: 33098

African (AFR) AF: 0.670 AC: 20426 AN: 30499

American (AMR) AF: 0.663 AC: 6937 AN: 10468

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 1943 AN: 2642

East Asian (EAS) AF: 0.778 AC: 2722 AN: 3499

South Asian (SAS) AF: 0.699 AC: 1862 AN: 2665

European-Finnish (FIN) AF: 0.730 AC: 4238 AN: 5807

Middle Eastern (MID) AF: 0.777 AC: 164 AN: 211

European-Non Finnish (NFE) AF: 0.716 AC: 37870 AN: 52900

Other (OTH) AF: 0.674 AC: 1018 AN: 1510

Alfa AF: 0.701 Hom.: 20423

Bravo AF: 0.692

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.33
PhyloP100		1.1
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: rs1882260; hg19: chrX-5808861;