X-5892643-G-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.*174C>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 0.111 in 567,548 control chromosomes in the GnomAD database, including 2,585 homozygotes. There are 18,925 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (543 hom., 3441 hem., cov: 23)
  • Exomes 𝑓: 0.11 (2042 hom. 15484 hem.)
• Consequence: NLGN4X NM_181332.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.08

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=-0.79).
• BP6: Variant X-5892643-G-T is Benign according to our data. Variant chrX-5892643-G-T is described in ClinVar as [Benign]. Clinvar id is 1266217.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN4X	NM_181332.3	c.*174C>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.*174C>A		3_prime_UTR_variant	6/6	1	NM_181332.3	P4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 12070 AN: 111086 Hom.: 542 Cov.: 23 AF XY: 0.103 AC XY: 3426 AN XY: 33300

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.0981

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.112 AC: 51083 AN: 456406 Hom.: 2042 Cov.: 7 AF XY: 0.114 AC XY: 15484 AN XY: 135784

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.0496

Gnomad4 ASJ exome AF: 0.0870

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.0915

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.109 AC: 12085 AN: 111142 Hom.: 543 Cov.: 23 AF XY: 0.103 AC XY: 3441 AN XY: 33366

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0735

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0867

Gnomad4 FIN AF: 0.0981

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.102

Alfa AF: 0.110 Hom.: 4010

Bravo AF: 0.110

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.4
Dann	Benign	0.64

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: rs3810687; hg19: chrX-5810684;