rs4370667

Positions:

• chrX-6049973-A-G
• chrX-6049973-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181332.3(NLGN4X):​c.473-20541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 110,400 control chromosomes in the GnomAD database, including 5,148 homozygotes. There are 11,174 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 0.35 (5148 hom., 11174 hem., cov: 22)
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.473-20541T>C		intron_variant		ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8	c.473-20541T>C		intron_variant		1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.353 AC: 38922 AN: 110352 Hom.: 5145 Cov.: 22 AF XY: 0.342 AC XY: 11151 AN XY: 32606

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.353 AC: 38945 AN: 110400 Hom.: 5148 Cov.: 22 AF XY: 0.342 AC XY: 11174 AN XY: 32664

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.374

Alfa AF: 0.360 Hom.: 2555

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.88
DANN	Benign	0.40

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: rs4370667; hg19: chrX-5968014;