rs1882260

Positions:

• chrX-5890820-G-A

Variant summary

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

The ENST00000381095.8(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 ENST00000381095.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.*1997C>T		3_prime_UTR_variant	6/6	ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8	c.*1997C>T		3_prime_UTR_variant	6/6	1	NM_181332.3	ENSP00000370485	P4
NLGN4X	ENST00000275857.10	c.*1997C>T		3_prime_UTR_variant	6/6	1		ENSP00000275857	P4
NLGN4X	ENST00000381093.6	c.*1997C>T		3_prime_UTR_variant	6/6	2		ENSP00000370483	P4
NLGN4X	ENST00000477079.1	n.277+12257C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.700 AC: 77556 AN: 110818 Hom.: 19038 Cov.: 23 AF XY: 0.703 AC XY: 23211 AN XY: 33038

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

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.660

Gnomad4 ASJ exome AF: 0.741

Gnomad4 EAS exome AF: 0.780

Gnomad4 SAS exome AF: 0.711

Gnomad4 FIN exome AF: 0.729

Gnomad4 NFE exome AF: 0.721

Gnomad4 OTH exome AF: 0.706

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

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.674

Alfa AF: 0.703 Hom.: 17469

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

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: rs1882260; hg19: chrX-5808861;