rs144247281

Variant names:

• chrX-71155230-T-C
• rs144247281
• NM_181303.2:c.594T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_181303.2(NLGN3):​c.594T>C​(p.Gly198Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,210,294 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 342 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., 20 hem., cov: 24)
  • Exomes 𝑓: 0.00079 (0 hom. 322 hem.)
• Consequence: NLGN3 NM_181303.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.523
• Publications: 1 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant X-71155230-T-C is Benign according to our data. Variant chrX-71155230-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.523 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 20 Unknown,XL gene

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.594T>C	p.Gly198Gly	synonymous	Exon 5 of 8	NP_851820.1
	NLGN3	NM_018977.4		c.534T>C	p.Gly178Gly	synonymous	Exon 4 of 7	NP_061850.2
	NLGN3	NM_001166660.2		c.474T>C	p.Gly158Gly	synonymous	Exon 3 of 6	NP_001160132.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN3	ENST00000358741.4	TSL:5 MANE Select	c.594T>C	p.Gly198Gly	synonymous	Exon 5 of 8	ENSP00000351591.4
	NLGN3	ENST00000374051.7	TSL:1	c.534T>C	p.Gly178Gly	synonymous	Exon 4 of 7	ENSP00000363163.3
	NLGN3	ENST00000395855.7	TSL:1	c.474T>C	p.Gly158Gly	synonymous	Exon 3 of 5	ENSP00000379196.3

Frequencies

GnomAD3 genomes AF: 0.000606 AC: 68 AN: 112138 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000187

Gnomad ASJ AF: 0.000379

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00148

Gnomad FIN AF: 0.000164

Gnomad MID AF: 0.0167

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000704 AC: 129 AN: 183298 AF XY: 0.000871

Gnomad AFR exome AF: 0.000228

Gnomad AMR exome AF: 0.000328

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000188

Gnomad NFE exome AF: 0.000868

Gnomad OTH exome AF: 0.000883

GnomAD4 exome AF: 0.000790 AC: 868 AN: 1098103 Hom.: 0 Cov.: 31 AF XY: 0.000886 AC XY: 322 AN XY: 363495

African (AFR) AF: 0.000227 AC: 6 AN: 26403

American (AMR) AF: 0.000227 AC: 8 AN: 35197

Ashkenazi Jewish (ASJ) AF: 0.000206 AC: 4 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00205 AC: 111 AN: 54133

European-Finnish (FIN) AF: 0.0000987 AC: 4 AN: 40532

Middle Eastern (MID) AF: 0.00219 AC: 9 AN: 4117

European-Non Finnish (NFE) AF: 0.000812 AC: 684 AN: 842049

Other (OTH) AF: 0.000911 AC: 42 AN: 46088

GnomAD4 genome AF: 0.000597 AC: 67 AN: 112191 Hom.: 0 Cov.: 24 AF XY: 0.000582 AC XY: 20 AN XY: 34379

African (AFR) AF: 0.000194 AC: 6 AN: 30898

American (AMR) AF: 0.000187 AC: 2 AN: 10713

Ashkenazi Jewish (ASJ) AF: 0.000379 AC: 1 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3546

South Asian (SAS) AF: 0.00111 AC: 3 AN: 2701

European-Finnish (FIN) AF: 0.000164 AC: 1 AN: 6116

Middle Eastern (MID) AF: 0.0183 AC: 4 AN: 219

European-Non Finnish (NFE) AF: 0.000941 AC: 50 AN: 53135

Other (OTH) AF: 0.00 AC: 0 AN: 1540

Alfa AF: 0.000727 Hom.: 7

Bravo AF: 0.000623

EpiCase AF: 0.00131

EpiControl AF: 0.00125

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	NLGN3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.4
DANN	Benign	0.69
PhyloP100		-0.52
Mutation Taster		=96/4	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: rs144247281; hg19: chrX-70375080;