Variant rs3817405 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032812.9(PLXDC2):c.1186G>A(p.Val396Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,611,310 control chromosomes in the GnomAD database, including 350,891 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.65 ( 32623 hom., cov: 29)

Exomes 𝑓: 0.66 ( 318268 hom. )

Consequence

PLXDC2
NM_032812.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54

Variant links:

Genes affected

PLXDC2 (HGNC:21013): (plexin domain containing 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLXDC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3601372E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PLXDC2	NM_032812.9 linkuse as main transcript	c.1186G>A	p.Val396Ile	missense_variant	11/14	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2 linkuse as main transcript	c.1039G>A	p.Val347Ile	missense_variant	10/13		NP_001269665.1
PLXDC2	XM_011519750.3 linkuse as main transcript	c.1186G>A	p.Val396Ile	missense_variant	11/14		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXDC2	ENST00000377252.5 linkuse as main transcript	c.1186G>A	p.Val396Ile	missense_variant	11/14	1	NM_032812.9	ENSP00000366460	P1	Q6UX71-1
PLXDC2	ENST00000377242.7 linkuse as main transcript	c.1039G>A	p.Val347Ile	missense_variant	10/13	1		ENSP00000366450		Q6UX71-2
PLXDC2	ENST00000377238.2 linkuse as main transcript	n.961G>A		non_coding_transcript_exon_variant	10/13	5

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98581

AN:

151460

Hom.:

32588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.697

Gnomad AMI

AF:

0.663

Gnomad AMR

AF:

0.537

Gnomad ASJ

AF:

0.750

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.619

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.676

GnomAD3 exomes

AF:

0.603

AC:

151147

AN:

250538

Hom.:

48140

AF XY:

0.615

AC XY:

83321

AN XY:

135426

show subpopulations

Gnomad AFR exome

AF:

0.700

Gnomad AMR exome

AF:

0.389

Gnomad ASJ exome

AF:

0.751

Gnomad EAS exome

AF:

0.290

Gnomad SAS exome

AF:

0.633

Gnomad FIN exome

AF:

0.616

Gnomad NFE exome

AF:

0.678

Gnomad OTH exome

AF:

0.659

GnomAD4 exome

AF:

0.656

AC:

956889

AN:

1459734

Hom.:

318268

Cov.:

AF XY:

0.657

AC XY:

476920

AN XY:

726224

show subpopulations

Gnomad4 AFR exome

AF:

0.699

Gnomad4 AMR exome

AF:

0.409

Gnomad4 ASJ exome

AF:

0.751

Gnomad4 EAS exome

AF:

0.357

Gnomad4 SAS exome

AF:

0.635

Gnomad4 FIN exome

AF:

0.615

Gnomad4 NFE exome

AF:

0.675

Gnomad4 OTH exome

AF:

0.659

GnomAD4 genome

AF:

0.651

AC:

98666

AN:

151576

Hom.:

32623

Cov.:

AF XY:

0.644

AC XY:

47682

AN XY:

74010

show subpopulations

Gnomad4 AFR

AF:

0.698

Gnomad4 AMR

AF:

0.536

Gnomad4 ASJ

AF:

0.750

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.608

Gnomad4 FIN

AF:

0.619

Gnomad4 NFE

AF:

0.675

Gnomad4 OTH

AF:

0.680

Alfa

AF:

0.673

Hom.:

83935

Bravo

AF:

0.645

TwinsUK

AF:

0.666

AC:

2471

ALSPAC

AF:

0.657

AC:

2534

ESP6500AA

AF:

0.692

AC:

3050

ESP6500EA

AF:

0.686

AC:

5903

ExAC

AF:

0.615

AC:

74674

Asia WGS

AF:

0.499

AC:

1734

AN:

3476

EpiCase

AF:

0.694

EpiControl

AF:

0.700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.0010

DANN

Benign

0.56

DEOGEN2

Benign

0.0075

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.082

T;T

MetaRNN

Benign

0.0000014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.21

N;N

REVEL

Benign

0.20

Sift

Benign

0.44

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0030

B;B

Vest4

0.065

MPC

0.015

ClinPred

0.019

GERP RS

-11

Varity_R

0.018

gMVP

0.17

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over