chrX-6054341-C-T

Position:

• chrX-6054341-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.473-24909G>A		intron_variant		ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8	c.473-24909G>A		intron_variant		1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 49475 AN: 110214 Hom.: 7983 Cov.: 23 AF XY: 0.448 AC XY: 14543 AN XY: 32480

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

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.438

Alfa AF: 0.464 Hom.: 10252

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

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: rs1882411; hg19: chrX-5972382;