rs5916338

Positions:

• chrX-6217488-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181332.3(NLGN4X):​c.-306+11053T>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 0.68 (19374 hom., 22224 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.-306+11053T>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.-306+11053T>C		intron_variant		1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.682 AC: 75416 AN: 110514 Hom.: 19367 Cov.: 23 AF XY: 0.678 AC XY: 22172 AN XY: 32716

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.609

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.648

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: 0.683 AC: 75475 AN: 110563 Hom.: 19374 Cov.: 23 AF XY: 0.678 AC XY: 22224 AN XY: 32775

Gnomad4 AFR AF: 0.919

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.646

Alfa AF: 0.655 Hom.: 5898

Bravo AF: 0.695

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.4
DANN	Benign	0.69

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: rs5916338; hg19: chrX-6135529;