Variant 3-129586617-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_015103.3(PLXND1):c.1591G>A(p.Gly531Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0415 in 1,573,692 control chromosomes in the GnomAD database, including 2,174 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G531V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.062 ( 444 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1730 hom. )

Consequence

PLXND1
NM_015103.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.17

Variant links:

Genes affected

PLXND1 (HGNC:9107): (plexin D1) Enables protein domain specific binding activity. Predicted to be involved in several processes, including endothelial cell migration; nervous system development; and regulation of angiogenesis. Predicted to act upstream of or within several processes, including circulatory system development; dichotomous subdivision of terminal units involved in salivary gland branching; and positive regulation of protein binding activity. Located in lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

PLXND1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013563931).

BP6

Variant 3-129586617-C-T is Benign according to our data. Variant chr3-129586617-C-T is described in ClinVar as [Benign]. Clinvar id is 3055714.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXND1	NM_015103.3 linkuse as main transcript	c.1591G>A	p.Gly531Ser	missense_variant	3/36	ENST00000324093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXND1	ENST00000324093.9 linkuse as main transcript	c.1591G>A	p.Gly531Ser	missense_variant	3/36	1	NM_015103.3	P1	Q9Y4D7-1
PLXND1	ENST00000505237.2 linkuse as main transcript	c.280G>A	p.Gly94Ser	missense_variant	2/4	5
PLXND1	ENST00000505665.5 linkuse as main transcript	c.70G>A	p.Gly24Ser	missense_variant, NMD_transcript_variant	1/5	5

Frequencies

GnomAD3 genomes

AF:

0.0620

AC:

9427

AN:

152050

Hom.:

443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0429

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0835

Gnomad FIN

AF:

0.0345

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0309

Gnomad OTH

AF:

0.0657

GnomAD3 exomes

AF:

0.0557

AC:

10429

AN:

187268

Hom.:

439

AF XY:

0.0564

AC XY:

5600

AN XY:

99278

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.0313

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.123

Gnomad SAS exome

AF:

0.0788

Gnomad FIN exome

AF:

0.0373

Gnomad NFE exome

AF:

0.0318

Gnomad OTH exome

AF:

0.0591

GnomAD4 exome

AF:

0.0393

AC:

55890

AN:

1421526

Hom.:

1730

Cov.:

AF XY:

0.0408

AC XY:

28643

AN XY:

702854

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.0324

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.121

Gnomad4 SAS exome

AF:

0.0816

Gnomad4 FIN exome

AF:

0.0368

Gnomad4 NFE exome

AF:

0.0278

Gnomad4 OTH exome

AF:

0.0562

GnomAD4 genome

AF:

0.0621

AC:

9444

AN:

152166

Hom.:

444

Cov.:

AF XY:

0.0632

AC XY:

4702

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.0428

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.0836

Gnomad4 FIN

AF:

0.0345

Gnomad4 NFE

AF:

0.0309

Gnomad4 OTH

AF:

0.0669

Alfa

AF:

0.0446

Hom.:

591

Bravo

AF:

0.0649

TwinsUK

AF:

0.0283

AC:

105

ALSPAC

AF:

0.0278

AC:

107

ESP6500AA

AF:

0.106

AC:

465

ESP6500EA

AF:

0.0326

AC:

280

ExAC

AF:

0.0435

AC:

5176

Asia WGS

AF:

0.113

AC:

390

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLXND1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.056

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.86

D;D

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.85

N;.

MutationTaster

Benign

0.94

P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

0.63

N;N

REVEL

Benign

0.052

Sift

Benign

0.67

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.068

B;.

Vest4

0.028

MPC

0.29

ClinPred

0.0039

GERP RS

1.2

Varity_R

0.045

gMVP

0.36

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over