X-71167078-A-C

Position:

• chrX-71167078-A-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_181303.2(NLGN3):​c.981A>C​(p.Pro327Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,097,419 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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: not found (cov: 23)
  • Exomes 𝑓: 0.000011 (0 hom. 4 hem.)
• Consequence: NLGN3 NM_181303.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.608 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLGN3	NM_181303.2	c.981A>C	p.Pro327Pro	synonymous_variant	7/8	ENST00000358741.4	NP_851820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLGN3	ENST00000358741.4	c.981A>C	p.Pro327Pro	synonymous_variant	7/8	5	NM_181303.2	ENSP00000351591.4
NLGN3	ENST00000685718.1	n.*328A>C		non_coding_transcript_exon_variant	7/8			ENSP00000510514.1
NLGN3	ENST00000685718.1	n.*328A>C		3_prime_UTR_variant	7/8			ENSP00000510514.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1097419 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 4 AN XY: 362795

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000397

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.8
DANN	Benign	0.70

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: rs797045794; hg19: chrX-70386928;