chrX-71147770-G-C

Variant names:

• chrX-71147770-G-C
• rs372993497
• NM_181303.2:c.21G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_181303.2(NLGN3):​c.21G>C​(p.Pro7Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,093,859 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. Synonymous variant affecting the same amino acid position (i.e. P7P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: NLGN3 NM_181303.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.031 with no splicing effect.

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.21G>C	p.Pro7Pro	synonymous	Exon 2 of 8	NP_851820.1	X5DNV3
	NLGN3	NM_018977.4		c.21G>C	p.Pro7Pro	synonymous	Exon 2 of 7	NP_061850.2	Q9NZ94-2
	NLGN3	NM_001166660.2		c.21G>C	p.Pro7Pro	synonymous	Exon 2 of 6	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.21G>C	p.Pro7Pro	synonymous	Exon 2 of 8	ENSP00000351591.4	Q9NZ94-1
	NLGN3	ENST00000374051.7	TSL:1	c.21G>C	p.Pro7Pro	synonymous	Exon 2 of 7	ENSP00000363163.3	Q9NZ94-2
	NLGN3	ENST00000395855.7	TSL:1	c.21G>C	p.Pro7Pro	synonymous	Exon 2 of 5	ENSP00000379196.3	E7EVK0

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1093859 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 1 AN XY: 360287

African (AFR) AF: 0.0000380 AC: 1 AN: 26316

American (AMR) AF: 0.00 AC: 0 AN: 34914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19328

East Asian (EAS) AF: 0.00 AC: 0 AN: 30028

South Asian (SAS) AF: 0.00 AC: 0 AN: 53525

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39229

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3951

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840690

Other (OTH) AF: 0.00 AC: 0 AN: 45878

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.58
PhyloP100		-0.031

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: rs372993497; hg19: chrX-70367620;