rs6638575

chrX-5894600-A-G

Variant summary

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

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

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High Homozygotes in GnomAd at 18486 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN4X	NM_181332.3	c.1602-934T>C		intron_variant		ENST00000381095.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN4X	ENST00000381095.8	c.1602-934T>C		intron_variant		1	NM_181332.3	P4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 75801 AN: 110111 Hom.: 18486 Cov.: 22 AF XY: 0.689 AC XY: 22316 AN XY: 32375

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

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.668

Alfa AF: 0.711 Hom.: 35656

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

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: rs6638575; hg19: chrX-5812641;