rs3810686

Variant names:

• chrX-5892533-C-A
• rs3810686
• NM_181332.3:c.*284G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-5892533-C-A
• chrX-5892533-C-G
• chrX-5892533-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_181332.3(NLGN4X):​c.*284G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 331,497 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 96 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 0.00083 (0 hom., 22 hem., cov: 23)
  • Exomes 𝑓: 0.0012 (0 hom. 74 hem.)
• Consequence: NLGN4X NM_181332.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 7 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BS2: High Hemizygotes in GnomAd4 at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4X	NM_181332.3	c.*284G>T		3_prime_UTR_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.*284G>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_181332.3	ENSP00000370485.3

Frequencies

GnomAD3 genomes AF: 0.000829 AC: 92 AN: 110960 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000171

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.000668

GnomAD4 exome AF: 0.00118 AC: 261 AN: 220481 Hom.: 0 Cov.: 2 AF XY: 0.00113 AC XY: 74 AN XY: 65619

African (AFR) AF: 0.000414 AC: 3 AN: 7248

American (AMR) AF: 0.000183 AC: 2 AN: 10955

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6437

East Asian (EAS) AF: 0.00 AC: 0 AN: 13477

South Asian (SAS) AF: 0.00205 AC: 46 AN: 22406

European-Finnish (FIN) AF: 0.000518 AC: 6 AN: 11580

Middle Eastern (MID) AF: 0.00225 AC: 2 AN: 887

European-Non Finnish (NFE) AF: 0.00141 AC: 189 AN: 134417

Other (OTH) AF: 0.000994 AC: 13 AN: 13074

GnomAD4 genome AF: 0.000829 AC: 92 AN: 111016 Hom.: 0 Cov.: 23 AF XY: 0.000662 AC XY: 22 AN XY: 33240

African (AFR) AF: 0.000130 AC: 4 AN: 30687

American (AMR) AF: 0.000191 AC: 2 AN: 10472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3498

South Asian (SAS) AF: 0.00 AC: 0 AN: 2600

European-Finnish (FIN) AF: 0.000171 AC: 1 AN: 5843

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00159 AC: 84 AN: 52867

Other (OTH) AF: 0.000660 AC: 1 AN: 1516

Alfa AF: 0.00000285 Hom.: 45347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.51
PhyloP100		-0.0070
Mutation Taster		=100/0	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: rs3810686; hg19: chrX-5810574;