rs200042650

chrX-154464420-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_017514.5(PLXNA3):c.1847G>A(p.Arg616Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000703 in 1,209,788 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., 4 hem., cov: 25)
  • Exomes 𝑓: 0.000069 (0 hom. 23 hem.)
• Consequence: PLXNA3 NM_017514.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0620

Genes affected

PLXNA3 (HGNC:9101): (plexin A3) This gene encodes a member of the plexin class of proteins. The encoded protein is a class 3 semaphorin receptor, and may be involved in cytoskeletal remodeling and as well as apoptosis. Studies of a similar gene in zebrafish suggest that it is important for axon pathfinding in the developing nervous system. This gene may be associated with tumor progression. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.033907056).
• BP6: Variant X-154464420-G-A is Benign according to our data. Variant chrX-154464420-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 208405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA3	NM_017514.5	c.1847G>A	p.Arg616Gln	missense_variant	9/33	ENST00000369682.4
PLXNA3	XM_047442247.1	c.1847G>A	p.Arg616Gln	missense_variant	9/22
PLXNA3	XR_007068193.1	n.2022G>A		non_coding_transcript_exon_variant	9/32
PLXNA3	XR_430556.4	n.2022G>A		non_coding_transcript_exon_variant	9/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA3	ENST00000369682.4	c.1847G>A	p.Arg616Gln	missense_variant	9/33	1	NM_017514.5	P1
PLXNA3	ENST00000482598.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000798 AC: 9 AN: 112795 Hom.: 0 Cov.: 25 AF XY: 0.000114 AC XY: 4 AN XY: 34953

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000185

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000359

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000940

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000824 AC: 15 AN: 182066 Hom.: 0 AF XY: 0.0000596 AC XY: 4 AN XY: 67112

Gnomad AFR exome AF: 0.000153

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000210

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000986

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.0000693 AC: 76 AN: 1096940 Hom.: 0 Cov.: 32 AF XY: 0.0000634 AC XY: 23 AN XY: 362708

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000739

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000784

Gnomad4 OTH exome AF: 0.0000651

GnomAD4 genome AF: 0.0000798 AC: 9 AN: 112848 Hom.: 0 Cov.: 25 AF XY: 0.000114 AC XY: 4 AN XY: 35016

Gnomad4 AFR AF: 0.0000321

Gnomad4 AMR AF: 0.000185

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000360

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000940

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000125

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

PLXNA3-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Childhood-onset schizophrenia Benign:1

Benign, criteria provided, single submitter

research

Dr. Guy Rouleau's laboratory, McGill University

Jan 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.0
Dann	Benign	0.91
FATHMM_MKL	Benign	0.094	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	0.95	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.027
Sift	Benign	0.50	T
Sift4G	Benign	0.82	T
Vest4		0.058
MVP		0.24
ClinPred		0.0066	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs200042650; hg19: chrX-153692763;