Variant X-154460254-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017514.5(PLXNA3):c.71G>A(p.Arg24His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000449 in 1,208,144 control chromosomes in the GnomAD database, including 2 homozygotes. There are 143 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 Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R24C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., 66 hem., cov: 25)

Exomes 𝑓: 0.00026 ( 1 hom. 77 hem. )

Consequence

PLXNA3
NM_017514.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.252

Variant links:

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]

PLXNA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004250586).

BP6

Variant X-154460254-G-A is Benign according to our data. Variant chrX-154460254-G-A is described in ClinVar as [Benign]. Clinvar id is 720976.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 66 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLXNA3	NM_017514.5 linkuse as main transcript	c.71G>A	p.Arg24His	missense_variant	2/33	ENST00000369682.4
PLXNA3	XM_047442247.1 linkuse as main transcript	c.71G>A	p.Arg24His	missense_variant	2/22
PLXNA3	XR_007068193.1 linkuse as main transcript	n.246G>A		non_coding_transcript_exon_variant	2/32
PLXNA3	XR_430556.4 linkuse as main transcript	n.246G>A		non_coding_transcript_exon_variant	2/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA3	ENST00000369682.4 linkuse as main transcript	c.71G>A	p.Arg24His	missense_variant	2/33	1	NM_017514.5	P1
PLXNA3	ENST00000495040.1 linkuse as main transcript	n.146-845G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

258

AN:

112243

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

AN XY:

34439

show subpopulations

Gnomad AFR

AF:

0.00726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00289

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:

0.00

Gnomad OTH

AF:

0.00200

GnomAD3 exomes

AF:

0.000754

AC:

136

AN:

180395

Hom.:

AF XY:

0.000484

AC XY:

AN XY:

66151

show subpopulations

Gnomad AFR exome

AF:

0.00845

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000502

Gnomad OTH exome

AF:

0.000674

GnomAD4 exome

AF:

0.000260

AC:

285

AN:

1095849

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

AN XY:

361787

show subpopulations

Gnomad4 AFR exome

AF:

0.00740

Gnomad4 AMR exome

AF:

0.000881

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.000804

GnomAD4 genome

AF:

0.00230

AC:

258

AN:

112295

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

AN XY:

34501

show subpopulations

Gnomad4 AFR

AF:

0.00724

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00198

Alfa

AF:

0.000535

Hom.:

Bravo

AF:

0.00370

ESP6500AA

AF:

0.00756

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000783

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PLXNA3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 26, 2019

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.71

M_CAP

Benign

0.011

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.93

MutationTaster

Benign

0.95

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.3

REVEL

Benign

0.032

Sift

Benign

0.082

Sift4G

Benign

0.15

Vest4

0.11

MVP

0.21

ClinPred

0.0065

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over