X-71147478-A-G

Position:

• chrX-71147478-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN3	NM_181303.2	c.-200-72A>G		intron_variant		ENST00000358741.4
LOC124905197	XR_007068262.1	n.1106+2805T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN3	ENST00000358741.4	c.-200-72A>G		intron_variant		5	NM_181303.2	A1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 62545 AN: 109484 Hom.: 14052 Cov.: 22 AF XY: 0.552 AC XY: 17519 AN XY: 31748

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

Gnomad4 AFR exome AF: 0.813

Gnomad4 AMR exome AF: 0.601

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.519

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

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.603

Alfa AF: 0.411 Hom.: 5519

Bravo AF: 0.597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
DANN	Benign	0.47

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: rs11795613; hg19: chrX-70367328;