chrX-5892533-C-T

Position:

• chrX-5892533-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_181332.3(NLGN4X):​c.*284G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 331,094 control chromosomes in the GnomAD database, including 18,698 homozygotes. There are 38,258 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (4931 hom., 10746 hem., cov: 23)
  • Exomes 𝑓: 0.41 (13767 hom. 27512 hem.)
• Consequence: NLGN4X NM_181332.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant X-5892533-C-T is Benign according to our data. Variant chrX-5892533-C-T is described in ClinVar as [Benign]. Clinvar id is 1251892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN4X	NM_181332.3	c.*284G>A		3_prime_UTR_variant	6/6	ENST00000381095.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN4X	ENST00000381095.8	c.*284G>A		3_prime_UTR_variant	6/6	1	NM_181332.3	P4

Frequencies

GnomAD3 genomes AF: 0.319 AC: 35416 AN: 110912 Hom.: 4932 Cov.: 23 AF XY: 0.324 AC XY: 10745 AN XY: 33150

Gnomad AFR AF: 0.0739

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.412 AC: 90738 AN: 220126 Hom.: 13767 Cov.: 2 AF XY: 0.419 AC XY: 27512 AN XY: 65596

Gnomad4 AFR exome AF: 0.0747

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.422

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.319 AC: 35410 AN: 110968 Hom.: 4931 Cov.: 23 AF XY: 0.324 AC XY: 10746 AN XY: 33216

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.327

Alfa AF: 0.401 Hom.: 36479

Bravo AF: 0.303

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.23
DANN	Benign	0.51

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: rs3810686; hg19: chrX-5810574;