X-6056512-G-A

Variant names:

• chrX-6056512-G-A
• rs6654813
• NM_181332.3:c.473-27080C>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.473-27080C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 110,074 control chromosomes in the GnomAD database, including 7,448 homozygotes. There are 13,197 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 0.42 (7448 hom., 13197 hem., cov: 22)
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.473-27080C>T		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.473-27080C>T		intron_variant	Intron 2 of 5	1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.422 AC: 46439 AN: 110032 Hom.: 7439 Cov.: 22

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.422 AC: 46477 AN: 110074 Hom.: 7448 Cov.: 22 AF XY: 0.407 AC XY: 13197 AN XY: 32410

African (AFR) AF: 0.530 AC: 16061 AN: 30290

American (AMR) AF: 0.396 AC: 4105 AN: 10365

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 861 AN: 2630

East Asian (EAS) AF: 0.216 AC: 750 AN: 3466

South Asian (SAS) AF: 0.327 AC: 843 AN: 2580

European-Finnish (FIN) AF: 0.336 AC: 1910 AN: 5679

Middle Eastern (MID) AF: 0.295 AC: 62 AN: 210

European-Non Finnish (NFE) AF: 0.393 AC: 20719 AN: 52680

Other (OTH) AF: 0.447 AC: 672 AN: 1504

Alfa AF: 0.218 Hom.: 1044

Bravo AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.012
DANN	Benign	0.41
PhyloP100		-0.54
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: rs6654813; hg19: chrX-5974553;