rs5916271

Variant names:

• chrX-5907687-A-C
• rs5916271
• NM_181332.3:c.811+1367T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181332.3(NLGN4X):​c.811+1367T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 109,803 control chromosomes in the GnomAD database, including 407 homozygotes. There are 2,788 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 0.091 (407 hom., 2788 hem., cov: 21)
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• autism, susceptibility to, X-linked 2

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.811+1367T>G		intron_variant	Intron 4 of 5	ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8	c.811+1367T>G		intron_variant	Intron 4 of 5	1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 9932 AN: 109746 Hom.: 402 Cov.: 21

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0644

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.0815

Gnomad NFE AF: 0.0920

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0906 AC: 9950 AN: 109803 Hom.: 407 Cov.: 21 AF XY: 0.0869 AC XY: 2788 AN XY: 32077

African (AFR) AF: 0.0559 AC: 1688 AN: 30213

American (AMR) AF: 0.142 AC: 1446 AN: 10213

Ashkenazi Jewish (ASJ) AF: 0.0644 AC: 170 AN: 2638

East Asian (EAS) AF: 0.165 AC: 562 AN: 3396

South Asian (SAS) AF: 0.193 AC: 489 AN: 2530

European-Finnish (FIN) AF: 0.0821 AC: 478 AN: 5823

Middle Eastern (MID) AF: 0.0798 AC: 17 AN: 213

European-Non Finnish (NFE) AF: 0.0920 AC: 4843 AN: 52613

Other (OTH) AF: 0.0974 AC: 145 AN: 1489

Alfa AF: 0.0994 Hom.: 534

Bravo AF: 0.0952

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.43
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5916271; hg19: chrX-5825728;