X-71151724-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_181303.2(NLGN3):c.518-1753T>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 0.51 (10350 hom., 16467 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: NLGN3 NM_181303.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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]

LOC124905197 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS2: High Homozygotes in GnomAd at 10353 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN3	NM_181303.2	c.518-1753T>G		intron_variant		ENST00000358741.4
LOC124905197	XR_007068262.1	n.597A>C		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN3	ENST00000358741.4	c.518-1753T>G		intron_variant		5	NM_181303.2	A1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 56205 AN: 110999 Hom.: 10353 Cov.: 23 AF XY: 0.495 AC XY: 16428 AN XY: 33201

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.555

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: 0.506 AC: 56238 AN: 111053 Hom.: 10350 Cov.: 23 AF XY: 0.495 AC XY: 16467 AN XY: 33265

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.563

Alfa AF: 0.412 Hom.: 3657

Bravo AF: 0.522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.0080
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs4844286; hg19: chrX-70371574;