NM_017514.5:c.1847G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0620

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 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 Benign. ClinVar VariationId is 208405.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA3	NM_017514.5 link	c.1847G>A	p.Arg616Gln	missense_variant	Exon 9 of 33	ENST00000369682.4	NP_059984.3	P51805
PLXNA3	XM_047442247.1 link	c.1847G>A	p.Arg616Gln	missense_variant	Exon 9 of 22		XP_047298203.1
PLXNA3	XR_007068193.1 link	n.2022G>A		non_coding_transcript_exon_variant	Exon 9 of 32
PLXNA3	XR_430556.4 link	n.2022G>A		non_coding_transcript_exon_variant	Exon 9 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA3	ENST00000369682.4 link	c.1847G>A	p.Arg616Gln	missense_variant	Exon 9 of 33	1	NM_017514.5	ENSP00000358696.3		P51805
PLXNA3	ENST00000482598.1 link	n.-29G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000798

AC:

AN:

112795

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0000824

AC:

AN:

182066

AF XY:

0.0000596

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000986

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000693

AC:

AN:

1096940

Hom.:

Cov.:

AF XY:

0.0000634

AC XY:

AN XY:

362708

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26390

American (AMR)

AF:

0.0000284

AC:

AN:

35182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19366

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.0000739

AC:

AN:

54136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39807

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.0000784

AC:

AN:

841658

Other (OTH)

AF:

0.0000651

AC:

AN:

46064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000798

AC:

AN:

112848

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

35016

show subpopulations

African (AFR)

AF:

0.0000321

AC:

AN:

31124

American (AMR)

AF:

0.000185

AC:

AN:

10807

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2661

East Asian (EAS)

AF:

0.00

AC:

AN:

3562

South Asian (SAS)

AF:

0.000360

AC:

AN:

2780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6259

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000940

AC:

AN:

53205

Other (OTH)

AF:

0.00

AC:

AN:

1549

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PLXNA3-related disorder

Benign:1

Jun 11, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Jan 01, 2014

Dr. Guy Rouleau's laboratory, McGill University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.0

(source)

DANN

Benign

0.91

FATHMM_MKL

Benign

0.094

M_CAP

Benign

0.012

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.94

PhyloP100

0.062

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.18

REVEL

Benign

0.027

Sift

Benign

0.50

Sift4G

Benign

0.82

Vest4

0.058

MVP

0.24

ClinPred

0.0066

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.32

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over