X-6227814-C-T

Variant names:

• chrX-6227814-C-T
• rs2290488
• ENST00000275857.10:c.-431G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020742.4(NLGN4X):​c.-431G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 21)
• Consequence: NLGN4X NM_020742.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 6 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)

LOC105373156 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020742.4. 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.-306+727G>A		intron	N/A	NP_851849.1	Q8N0W4-1
	NLGN4X	NM_020742.4		c.-431G>A		5_prime_UTR	Exon 1 of 6	NP_065793.1	Q8N0W4-1
	NLGN4X	NM_001282145.2		c.-613+727G>A		intron	N/A	NP_001269074.1	Q8N0W4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4X	ENST00000275857.10	TSL:1	c.-431G>A		5_prime_UTR	Exon 1 of 6	ENSP00000275857.6	Q8N0W4-1
	NLGN4X	ENST00000381095.8	TSL:1 MANE Select	c.-306+727G>A		intron	N/A	ENSP00000370485.3	Q8N0W4-1
	NLGN4X	ENST00000381092.1	TSL:2	c.-613+727G>A		intron	N/A	ENSP00000370482.1	Q8N0W4-1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 2028

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.29
DANN	Benign	0.78
PhyloP100		-0.059
PromoterAI		0.039	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.44		Position offset: -2

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

Other links and lift over

dbSNP: rs2290488; hg19: chrX-6145855;