X-5970597-C-T

Variant names:

• chrX-5970597-C-T
• rs1921361
• NM_181332.3:c.625+58683G>A

Variant summary

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

The NM_181332.3(NLGN4X):​c.625+58683G>A 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 0.63 (15562 hom., 20464 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• 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=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.625+58683G>A		intron_variant	Intron 3 of 5	ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8	c.625+58683G>A		intron_variant	Intron 3 of 5	1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.630 AC: 69457 AN: 110322 Hom.: 15568 Cov.: 23

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.686

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.588

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: 0.629 AC: 69470 AN: 110375 Hom.: 15562 Cov.: 23 AF XY: 0.627 AC XY: 20464 AN XY: 32615

African (AFR) AF: 0.680 AC: 20683 AN: 30395

American (AMR) AF: 0.595 AC: 6180 AN: 10384

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 1759 AN: 2627

East Asian (EAS) AF: 0.597 AC: 2079 AN: 3481

South Asian (SAS) AF: 0.612 AC: 1598 AN: 2612

European-Finnish (FIN) AF: 0.631 AC: 3628 AN: 5749

Middle Eastern (MID) AF: 0.677 AC: 147 AN: 217

European-Non Finnish (NFE) AF: 0.612 AC: 32285 AN: 52738

Other (OTH) AF: 0.587 AC: 884 AN: 1505

Alfa AF: 0.616 Hom.: 47543

Bravo AF: 0.628

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.22
PhyloP100		-0.034
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: rs1921361; hg19: chrX-5888638;