rs11795613

Variant names:

• chrX-71147478-A-G
• rs11795613
• NM_181303.2:c.-200-72A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181303.2(NLGN3):​c.-200-72A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 312,174 control chromosomes in the GnomAD database, including 24,418 homozygotes. There are 49,617 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 0.57 (14055 hom., 17566 hem., cov: 22)
  • Exomes 𝑓: 0.48 (24418 hom. 49617 hem.)
  • Failed GnomAD Quality Control
• Consequence: NLGN3 NM_181303.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814
• 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: 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

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.-200-72A>G		intron	N/A	NP_851820.1	X5DNV3
	NLGN3	NM_018977.4		c.-200-72A>G		intron	N/A	NP_061850.2	Q9NZ94-2
	NLGN3	NM_001166660.2		c.-200-72A>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.-200-72A>G		intron	N/A	ENSP00000351591.4	Q9NZ94-1
	NLGN3	ENST00000374051.7	TSL:1	c.-200-72A>G		intron	N/A	ENSP00000363163.3	Q9NZ94-2
	NLGN3	ENST00000395855.7	TSL:1	c.-200-72A>G		intron	N/A	ENSP00000379196.3	E7EVK0

Frequencies

GnomAD3 genomes AF: 0.571 AC: 62545 AN: 109484 Hom.: 14052 Cov.: 22

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.648

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.476 AC: 148623 AN: 312174 Hom.: 24418 AF XY: 0.477 AC XY: 49617 AN XY: 104012

African (AFR) AF: 0.813 AC: 7631 AN: 9391

American (AMR) AF: 0.601 AC: 8190 AN: 13635

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 5516 AN: 9569

East Asian (EAS) AF: 0.324 AC: 7157 AN: 22057

South Asian (SAS) AF: 0.464 AC: 12216 AN: 26331

European-Finnish (FIN) AF: 0.410 AC: 8768 AN: 21395

Middle Eastern (MID) AF: 0.596 AC: 798 AN: 1338

European-Non Finnish (NFE) AF: 0.467 AC: 88543 AN: 189566

Other (OTH) AF: 0.519 AC: 9804 AN: 18892

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.571 AC: 62594 AN: 109536 Hom.: 14055 Cov.: 22 AF XY: 0.552 AC XY: 17566 AN XY: 31810

African (AFR) AF: 0.815 AC: 24455 AN: 29992

American (AMR) AF: 0.603 AC: 6210 AN: 10293

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1488 AN: 2624

East Asian (EAS) AF: 0.316 AC: 1090 AN: 3451

South Asian (SAS) AF: 0.439 AC: 1112 AN: 2532

European-Finnish (FIN) AF: 0.398 AC: 2279 AN: 5727

Middle Eastern (MID) AF: 0.651 AC: 140 AN: 215

European-Non Finnish (NFE) AF: 0.469 AC: 24652 AN: 52561

Other (OTH) AF: 0.603 AC: 896 AN: 1487

Alfa AF: 0.449 Hom.: 7533

Bravo AF: 0.597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
DANN	Benign	0.47
PhyloP100		-0.81
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: rs11795613; hg19: chrX-70367328;