X-5892715-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.*102G>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 0.315 in 1,112,611 control chromosomes in the GnomAD database, including 41,117 homozygotes. There are 106,097 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (6558 hom., 11781 hem., cov: 22)
  • Exomes 𝑓: 0.31 (34559 hom. 94316 hem.)
• Consequence: NLGN4X NM_181332.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.452

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=-0.97).
• BP6: Variant X-5892715-C-T is Benign according to our data. Variant chrX-5892715-C-T is described in ClinVar as [Benign]. Clinvar id is 1238862.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) 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.*102G>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.*102G>A		3_prime_UTR_variant	6/6	1	NM_181332.3	P4

Frequencies

GnomAD3 genomes AF: 0.378 AC: 41590 AN: 110091 Hom.: 6558 Cov.: 22 AF XY: 0.362 AC XY: 11736 AN XY: 32387

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.308 AC: 309113 AN: 1002466 Hom.: 34559 Cov.: 19 AF XY: 0.311 AC XY: 94316 AN XY: 302982

Gnomad4 AFR exome AF: 0.616

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.378 AC: 41630 AN: 110145 Hom.: 6558 Cov.: 22 AF XY: 0.363 AC XY: 11781 AN XY: 32451

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.339

Alfa AF: 0.329 Hom.: 2075

Bravo AF: 0.392

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	-0.97
Cadd	Benign	0.077
Dann	Benign	0.52

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: rs3810688; hg19: chrX-5810756; COSMIC: COSV52009610;