rs7051529

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-71154354-A-G
• chrX-71154354-A-T

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: XL, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181303.2. 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
	NLGN3	NM_181303.2	MANE Select	c.577+818A>G		intron	N/A	NP_851820.1	X5DNV3
	NLGN3	NM_018977.4		c.517+818A>G		intron	N/A	NP_061850.2	Q9NZ94-2
	NLGN3	NM_001166660.2		c.458-860A>G		intron	N/A	NP_001160132.1	X5D7L6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN3	ENST00000358741.4	TSL:5 MANE Select	c.577+818A>G		intron	N/A	ENSP00000351591.4	Q9NZ94-1
	NLGN3	ENST00000374051.7	TSL:1	c.517+818A>G		intron	N/A	ENSP00000363163.3	Q9NZ94-2
	NLGN3	ENST00000395855.7	TSL:1	c.458-860A>G		intron	N/A	ENSP00000379196.3	E7EVK0

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

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