rs1232376219

Variant names:

• chrX-5892878-G-C
• rs1232376219
• NM_181332.3:c.2390C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-5892878-G-C
• chrX-5892878-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181332.3(NLGN4X):​c.2390C>G​(p.Thr797Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T797N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: NLGN4X NM_181332.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.64
• 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26913065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.2390C>G	p.Thr797Ser	missense_variant	Exon 6 of 6	ENST00000381095.8	NP_851849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN4X	ENST00000381095.8	c.2390C>G	p.Thr797Ser	missense_variant	Exon 6 of 6	1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.27	T;T;T;.;T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.83	.;T;.;T;.
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.2	L;L;L;.;L
PhyloP100		6.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.6	N;.;N;.;N
REVEL	Benign	0.13
Sift	Benign	0.038	D;.;D;.;D
Sift4G	Benign	0.25	T;T;T;.;T
Polyphen		0.039	B;B;B;B;B
Vest4		0.23
MVP		0.77
MPC		1.0
ClinPred		0.46	T
GERP RS		3.8
Varity_R		0.18
gMVP		0.54
Mutation Taster		=88/12	polymorphism

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: rs1232376219; hg19: chrX-5810919;