rs4844286

Variant names:

• chrX-71151724-T-A
• rs4844286
• NM_181303.2:c.518-1753T>A

Your query was ambiguous. Multiple possible variants found:

• chrX-71151724-T-A
• chrX-71151724-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181303.2(NLGN3):​c.518-1753T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 111,060 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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 0.000018 (0 hom., 1 hem., cov: 23)
• Consequence: NLGN3 NM_181303.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 5 publications found

Genes affected

NLGN3 (HGNC:14289): (neuroligin 3) This gene encodes a member of 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. Mutations in this gene may be associated with autism and Asperger syndrome. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Oct 2009]

NLGN3 Gene-Disease associations (from GenCC):

• autism, susceptibility to, X-linked 1

  Inheritance: Unknown, XL Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: MODERATE Submitted by: Illumina, ClinGen

LOC124905197 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN3	NM_181303.2	c.518-1753T>A		intron_variant	Intron 3 of 7	ENST00000358741.4	NP_851820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN3	ENST00000358741.4	c.518-1753T>A		intron_variant	Intron 3 of 7	5	NM_181303.2	ENSP00000351591.4
NLGN3	ENST00000685718.1	n.458-1753T>A		intron_variant	Intron 2 of 7			ENSP00000510514.1

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111060 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111060 Hom.: 0 Cov.: 23 AF XY: 0.0000301 AC XY: 1 AN XY: 33230

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000656 AC: 2 AN: 30494

American (AMR) AF: 0.00 AC: 0 AN: 10504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3505

South Asian (SAS) AF: 0.00 AC: 0 AN: 2663

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52884

Other (OTH) AF: 0.00 AC: 0 AN: 1505

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 3657

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0080
DANN	Benign	0.19
PhyloP100		-2.7

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: rs4844286; hg19: chrX-70371574;