X-6054341-C-T

Variant names:

• chrX-6054341-C-T
• rs1882411
• NM_181332.3:c.473-24909G>A

Variant summary

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

The NM_181332.3(NLGN4X):​c.473-24909G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 110,268 control chromosomes in the GnomAD database, including 7,978 homozygotes. There are 14,553 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 0.45 (7978 hom., 14553 hem., cov: 23)
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.473-24909G>A		intron_variant	Intron 2 of 5	ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8	c.473-24909G>A		intron_variant	Intron 2 of 5	1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 49475 AN: 110214 Hom.: 7983 Cov.: 23

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.645

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.449 AC: 49466 AN: 110268 Hom.: 7978 Cov.: 23 AF XY: 0.447 AC XY: 14553 AN XY: 32542

African (AFR) AF: 0.386 AC: 11704 AN: 30314

American (AMR) AF: 0.440 AC: 4550 AN: 10332

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1490 AN: 2629

East Asian (EAS) AF: 0.615 AC: 2130 AN: 3464

South Asian (SAS) AF: 0.454 AC: 1186 AN: 2613

European-Finnish (FIN) AF: 0.484 AC: 2768 AN: 5723

Middle Eastern (MID) AF: 0.642 AC: 138 AN: 215

European-Non Finnish (NFE) AF: 0.468 AC: 24704 AN: 52801

Other (OTH) AF: 0.438 AC: 658 AN: 1501

Alfa AF: 0.461 Hom.: 15524

Bravo AF: 0.441

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.84
DANN	Benign	0.65
PhyloP100		-0.62
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: rs1882411; hg19: chrX-5972382;