chrX-5892533-C-A

Position:

• chrX-5892533-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_181332.3(NLGN4X):​c.*284G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 331,497 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 96 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 0.00083 (0 hom., 22 hem., cov: 23)
  • Exomes 𝑓: 0.0012 (0 hom. 74 hem.)
• Consequence: NLGN4X NM_181332.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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]

NLGN4X (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BS2: High Hemizygotes in GnomAd4 at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.*284G>T		3_prime_UTR_variant	6/6	ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095	c.*284G>T		3_prime_UTR_variant	6/6	1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.000829 AC: 92 AN: 110960 Hom.: 0 Cov.: 23 AF XY: 0.000663 AC XY: 22 AN XY: 33174

Gnomad AFR AF: 0.000131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000171

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.000668

GnomAD4 exome AF: 0.00118 AC: 261 AN: 220481 Hom.: 0 Cov.: 2 AF XY: 0.00113 AC XY: 74 AN XY: 65619

Gnomad4 AFR exome AF: 0.000414

Gnomad4 AMR exome AF: 0.000183

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00205

Gnomad4 FIN exome AF: 0.000518

Gnomad4 NFE exome AF: 0.00141

Gnomad4 OTH exome AF: 0.000994

GnomAD4 genome AF: 0.000829 AC: 92 AN: 111016 Hom.: 0 Cov.: 23 AF XY: 0.000662 AC XY: 22 AN XY: 33240

Gnomad4 AFR AF: 0.000130

Gnomad4 AMR AF: 0.000191

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000171

Gnomad4 NFE AF: 0.00159

Gnomad4 OTH AF: 0.000660

Alfa AF: 0.00000379 Hom.: 36479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
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;