NM_181332.3:c.473-52467A>G

Variant names:

• chrX-6081899-T-C
• rs10522049
• NM_181332.3:c.473-52467A>G

Variant summary

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

The NM_181332.3(NLGN4X):​c.473-52467A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 111,964 control chromosomes in the GnomAD database, including 127 homozygotes. There are 1,616 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 0.049 (127 hom., 1616 hem., cov: 23)
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.473-52467A>G		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.473-52467A>G		intron_variant	Intron 2 of 5	1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 5496 AN: 111906 Hom.: 126 Cov.: 23

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.0252

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0360

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

GnomAD4 genome AF: 0.0492 AC: 5510 AN: 111964 Hom.: 127 Cov.: 23 AF XY: 0.0473 AC XY: 1616 AN XY: 34162

African (AFR) AF: 0.0730 AC: 2253 AN: 30851

American (AMR) AF: 0.0278 AC: 294 AN: 10591

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 39 AN: 2655

East Asian (EAS) AF: 0.156 AC: 550 AN: 3530

South Asian (SAS) AF: 0.126 AC: 337 AN: 2684

European-Finnish (FIN) AF: 0.0309 AC: 186 AN: 6027

Middle Eastern (MID) AF: 0.0230 AC: 5 AN: 217

European-Non Finnish (NFE) AF: 0.0336 AC: 1787 AN: 53206

Other (OTH) AF: 0.0388 AC: 59 AN: 1521

Alfa AF: 0.0424 Hom.: 331

Bravo AF: 0.0496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.43
DANN	Benign	0.48
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: rs10522049; hg19: chrX-5999940;