rs5916271

Positions:

• chrX-5907687-A-C

Variant summary

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

The NM_181332.3(NLGN4X):​c.811+1367T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 109,803 control chromosomes in the GnomAD database, including 407 homozygotes. There are 2,788 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 0.091 (407 hom., 2788 hem., cov: 21)
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN4X	NM_181332.3	c.811+1367T>G		intron_variant		ENST00000381095.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN4X	ENST00000381095.8	c.811+1367T>G		intron_variant		1	NM_181332.3	P4

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 9932 AN: 109746 Hom.: 402 Cov.: 21 AF XY: 0.0868 AC XY: 2777 AN XY: 32010

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0644

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.0815

Gnomad NFE AF: 0.0920

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0906 AC: 9950 AN: 109803 Hom.: 407 Cov.: 21 AF XY: 0.0869 AC XY: 2788 AN XY: 32077

Gnomad4 AFR AF: 0.0559

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.0644

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.0821

Gnomad4 NFE AF: 0.0920

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.0994 Hom.: 534

Bravo AF: 0.0952

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.43

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: rs5916271; hg19: chrX-5825728;