rs376877146

Variant names:

• chrX-71147759-C-A
• rs376877146
• NM_181303.2:c.10C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-71147759-C-A
• chrX-71147759-C-T

Variant summary

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

The NM_181303.2(NLGN3):​c.10C>A​(p.Arg4Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,203,746 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.000080 (0 hom., 3 hem., cov: 22)
  • Exomes 𝑓: 0.0000055 (0 hom. 3 hem.)
• Consequence: NLGN3 NM_181303.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.547 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN3	NM_181303.2	c.10C>A	p.Arg4Arg	synonymous_variant	Exon 2 of 8	ENST00000358741.4	NP_851820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN3	ENST00000358741.4	c.10C>A	p.Arg4Arg	synonymous_variant	Exon 2 of 8	5	NM_181303.2	ENSP00000351591.4
NLGN3	ENST00000685718.1	n.10C>A		non_coding_transcript_exon_variant	Exon 2 of 8			ENSP00000510514.1

Frequencies

GnomAD3 genomes AF: 0.0000804 AC: 9 AN: 111878 Hom.: 0 Cov.: 22 AF XY: 0.0000881 AC XY: 3 AN XY: 34054

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.0103

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000377

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000550 AC: 6 AN: 1091868 Hom.: 0 Cov.: 31 AF XY: 0.00000837 AC XY: 3 AN XY: 358606

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000476

Gnomad4 OTH exome AF: 0.0000437

GnomAD4 genome AF: 0.0000804 AC: 9 AN: 111878 Hom.: 0 Cov.: 22 AF XY: 0.0000881 AC XY: 3 AN XY: 34054

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000377

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.2
DANN	Benign	0.85

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: rs376877146; hg19: chrX-70367609;