chrX-5893009-CCT-GCG

Variant names:

• chrX-5893009-CCT-GCG
• NM_181332.3:c.2257_2259delAGGinsCGC
• NLGN4X p.754

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_181332.3(NLGN4X):​c.2257_2259delAGGinsCGC​(p.754) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 21)
• Consequence: NLGN4X NM_181332.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.81
• Publications: 0 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181332.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4X	NM_181332.3	MANE Select	c.2257_2259delAGGinsCGC	p.754	synonymous	N/A	NP_851849.1	Q8N0W4-1
	NLGN4X	NM_001282145.2		c.2257_2259delAGGinsCGC	p.754	synonymous	N/A	NP_001269074.1	Q8N0W4-1
	NLGN4X	NM_001282146.2		c.2257_2259delAGGinsCGC	p.754	synonymous	N/A	NP_001269075.1	Q8N0W4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4X	ENST00000381095.8	TSL:1 MANE Select	c.2257_2259delAGGinsCGC	p.754	synonymous	N/A	ENSP00000370485.3	Q8N0W4-1
	NLGN4X	ENST00000538097.6	TSL:1	c.2317_2319delAGGinsCGC	p.774	synonymous	N/A	ENSP00000439203.3	Q8N0W4-2
	NLGN4X	ENST00000275857.10	TSL:1	c.2257_2259delAGGinsCGC	p.754	synonymous	N/A	ENSP00000275857.6	Q8N0W4-1

Frequencies

GnomAD3 genomes Cov.: 21

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

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-5811050;