Genetic Variant PLXND1:p.Gln1909Gln (chr3-129556363-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_015103.3(PLXND1):c.5727G>A(p.Gln1909Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,730 control chromosomes in the GnomAD database, including 20,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.19 ( 3157 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17184 hom. )

Consequence

PLXND1
NM_015103.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.650

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 3-129556363-C-T is Benign according to our data. Variant chr3-129556363-C-T is described in ClinVar as [Benign]. Clinvar id is 3059889.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXND1	NM_015103.3 link	c.5727G>A	p.Gln1909Gln	synonymous_variant	Exon 36 of 36	ENST00000324093.9	NP_055918.3	Q9Y4D7-1
PLXND1	XM_011512589.2 link	c.5337G>A	p.Gln1779Gln	synonymous_variant	Exon 33 of 33		XP_011510891.1
PLXND1	XM_011512592.1 link	c.2895G>A	p.Gln965Gln	synonymous_variant	Exon 24 of 24		XP_011510894.1
PLXND1	XM_011512588.3 link	c.*84G>A		3_prime_UTR_variant	Exon 36 of 36		XP_011510890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXND1	ENST00000324093.9 link	c.5727G>A	p.Gln1909Gln	synonymous_variant	Exon 36 of 36	1	NM_015103.3	ENSP00000317128.4		Q9Y4D7-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28432

AN:

152118

Hom.:

3140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.0829

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.168

AC:

42319

AN:

251442

Hom.:

4131

AF XY:

0.167

AC XY:

22681

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.288

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.223

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.0778

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.146

AC:

212675

AN:

1461494

Hom.:

17184

Cov.:

AF XY:

0.148

AC XY:

107617

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.297

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.163

Gnomad4 EAS exome

AF:

0.256

Gnomad4 SAS exome

AF:

0.233

Gnomad4 FIN exome

AF:

0.0794

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.187

AC:

28485

AN:

152236

Hom.:

3157

Cov.:

AF XY:

0.190

AC XY:

14118

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.289

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.0829

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.146

Hom.:

3382

Bravo

AF:

0.200

Asia WGS

AF:

0.223

AC:

778

AN:

3478

EpiCase

AF:

0.136

EpiControl

AF:

0.140

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLXND1-related disorder

Benign:1

Jun 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.38

CADD

Benign

5.6

DANN

Benign

0.88

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