X-71154354-A-G

Variant names:

• chrX-71154354-A-G
• rs7051529
• NM_181303.2:c.577+818A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181303.2(NLGN3):​c.577+818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.55 (13061 hom., 18681 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: NLGN3 NM_181303.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 2 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

ENSG00000228427 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN3	NM_181303.2	c.577+818A>G		intron_variant	Intron 4 of 7	ENST00000358741.4	NP_851820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN3	ENST00000358741.4	c.577+818A>G		intron_variant	Intron 4 of 7	5	NM_181303.2	ENSP00000351591.4
NLGN3	ENST00000685718.1	n.517+818A>G		intron_variant	Intron 3 of 7			ENSP00000510514.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 61929 AN: 111715 Hom.: 13060 Cov.: 24

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.607

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.561

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.555 AC: 61986 AN: 111768 Hom.: 13061 Cov.: 24 AF XY: 0.550 AC XY: 18681 AN XY: 33988

African (AFR) AF: 0.802 AC: 24740 AN: 30838

American (AMR) AF: 0.581 AC: 6222 AN: 10713

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1469 AN: 2645

East Asian (EAS) AF: 0.366 AC: 1267 AN: 3465

South Asian (SAS) AF: 0.468 AC: 1280 AN: 2736

European-Finnish (FIN) AF: 0.412 AC: 2514 AN: 6108

Middle Eastern (MID) AF: 0.606 AC: 132 AN: 218

European-Non Finnish (NFE) AF: 0.439 AC: 23228 AN: 52855

Other (OTH) AF: 0.569 AC: 870 AN: 1528

Alfa AF: 0.488 Hom.: 4529

Bravo AF: 0.576

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.99
DANN	Benign	0.65
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs7051529; hg19: chrX-70374204; COSMIC: COSV62445601;