chrX-5894600-A-G

Variant names:

• chrX-5894600-A-G
• rs6638575
• NM_181332.3:c.1602-934T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181332.3(NLGN4X):​c.1602-934T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.69 (18481 hom., 22357 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.1602-934T>C		intron_variant	Intron 5 of 5	ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8	c.1602-934T>C		intron_variant	Intron 5 of 5	1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.688 AC: 75801 AN: 110111 Hom.: 18486 Cov.: 22

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.781

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.670

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.688 AC: 75830 AN: 110164 Hom.: 18481 Cov.: 22 AF XY: 0.689 AC XY: 22357 AN XY: 32438

African (AFR) AF: 0.624 AC: 18879 AN: 30264

American (AMR) AF: 0.652 AC: 6747 AN: 10341

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 1943 AN: 2627

East Asian (EAS) AF: 0.784 AC: 2703 AN: 3446

South Asian (SAS) AF: 0.714 AC: 1828 AN: 2561

European-Finnish (FIN) AF: 0.728 AC: 4191 AN: 5757

Middle Eastern (MID) AF: 0.787 AC: 166 AN: 211

European-Non Finnish (NFE) AF: 0.719 AC: 37975 AN: 52801

Other (OTH) AF: 0.668 AC: 992 AN: 1485

Alfa AF: 0.704 Hom.: 48004

Bravo AF: 0.680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.74
DANN	Benign	0.50
PhyloP100		-0.75
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: rs6638575; hg19: chrX-5812641;