rs6529901

chrX-5937979-G-A

Variant summary

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

The NM_181332.3(NLGN4X):c.626-28740C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 110,804 control chromosomes in the GnomAD database, including 4,465 homozygotes. There are 10,036 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 0.30 (4465 hom., 10036 hem., cov: 23)
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748

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 (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN4X	NM_181332.3	c.626-28740C>T		intron_variant		ENST00000381095.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN4X	ENST00000381095.8	c.626-28740C>T		intron_variant		1	NM_181332.3	P4

Frequencies

GnomAD3 genomes AF: 0.301 AC: 33310 AN: 110754 Hom.: 4468 Cov.: 23 AF XY: 0.304 AC XY: 10033 AN XY: 32996

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.552

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.301 AC: 33303 AN: 110804 Hom.: 4465 Cov.: 23 AF XY: 0.304 AC XY: 10036 AN XY: 33056

Gnomad4 AFR AF: 0.0601

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.315

Alfa AF: 0.333 Hom.: 2873

Bravo AF: 0.286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.57
Dann	Benign	0.41

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: rs6529901; hg19: chrX-5856020;