Variant 3-129559648-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015103.3(PLXND1):c.5269G>A(p.Asp1757Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,610,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

PLXND1
NM_015103.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXND1	NM_015103.3 link	c.5269G>A	p.Asp1757Asn	missense_variant	32/36	ENST00000324093.9	NP_055918.3	Q9Y4D7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXND1	ENST00000324093.9 link	c.5269G>A	p.Asp1757Asn	missense_variant	32/36	1	NM_015103.3	ENSP00000317128.4		Q9Y4D7-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

248378

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

134118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000622

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000309

AC:

AN:

1458066

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

725176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152020

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.5269G>A (p.D1757N) alteration is located in exon 32 (coding exon 32) of the PLXND1 gene. This alteration results from a G to A substitution at nucleotide position 5269, causing the aspartic acid (D) at amino acid position 1757 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.2

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.35

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.70

MutPred

0.69

Gain of glycosylation at S1754 (P = 0.0608);

MVP

0.81

MPC

1.6

ClinPred

0.93

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.27

gMVP

0.63

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