Variant rs3816527 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002852.4(PTX3):c.143C>A(p.Ala48Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,603,296 control chromosomes in the GnomAD database, including 290,190 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.64 ( 32073 hom., cov: 32)

Exomes 𝑓: 0.59 ( 258117 hom. )

Consequence

PTX3
NM_002852.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86

Variant links:

Genes affected

PTX3 (HGNC:9692): (pentraxin 3) This gene encodes a member of the pentraxin protein family. The expression of this protein is induced by inflammatory cytokines in response to inflammatory stimuli in several mesenchymal and epithelial cell types, particularly endothelial cells and mononuclear phagocytes. The protein promotes fibrocyte differentiation and is involved in regulating inflammation and complement activation. It also plays a role in angiogenesis and tissue remodeling. The protein serves as a biomarker for several inflammatory conditions. [provided by RefSeq, Jun 2016]

PTX3 links:

VEPH1 (HGNC:25735): (ventricular zone expressed PH domain containing 1) Predicted to enable phosphatidylinositol-5-phosphate binding activity. Involved in negative regulation of SMAD protein signal transduction and negative regulation of transforming growth factor beta receptor signaling pathway. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

VEPH1 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=1.051613E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTX3	NM_002852.4 linkuse as main transcript	c.143C>A	p.Ala48Asp	missense_variant	2/3	ENST00000295927.4	NP_002843.2	P26022
VEPH1	NM_001167912.2 linkuse as main transcript	c.530-9037G>T		intron_variant		ENST00000362010.7	NP_001161384.1	Q14D04-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTX3	ENST00000295927.4 linkuse as main transcript	c.143C>A	p.Ala48Asp	missense_variant	2/3	1	NM_002852.4	ENSP00000295927.3		P26022
VEPH1	ENST00000362010.7 linkuse as main transcript	c.530-9037G>T		intron_variant		1	NM_001167912.2	ENSP00000354919.2		Q14D04-1

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97822

AN:

151930

Hom.:

32017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.656

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.791

Gnomad SAS

AF:

0.728

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.576

Gnomad OTH

AF:

0.621

GnomAD3 exomes

AF:

0.636

AC:

146834

AN:

230906

Hom.:

47434

AF XY:

0.633

AC XY:

79940

AN XY:

126254

show subpopulations

Gnomad AFR exome

AF:

0.728

Gnomad AMR exome

AF:

0.701

Gnomad ASJ exome

AF:

0.529

Gnomad EAS exome

AF:

0.785

Gnomad SAS exome

AF:

0.698

Gnomad FIN exome

AF:

0.638

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.599

GnomAD4 exome

AF:

0.593

AC:

860403

AN:

1451248

Hom.:

258117

Cov.:

AF XY:

0.595

AC XY:

429357

AN XY:

721160

show subpopulations

Gnomad4 AFR exome

AF:

0.733

Gnomad4 AMR exome

AF:

0.700

Gnomad4 ASJ exome

AF:

0.532

Gnomad4 EAS exome

AF:

0.823

Gnomad4 SAS exome

AF:

0.699

Gnomad4 FIN exome

AF:

0.634

Gnomad4 NFE exome

AF:

0.567

Gnomad4 OTH exome

AF:

0.600

GnomAD4 genome

AF:

0.644

AC:

97947

AN:

152048

Hom.:

32073

Cov.:

AF XY:

0.650

AC XY:

48297

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.730

Gnomad4 AMR

AF:

0.672

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.791

Gnomad4 SAS

AF:

0.727

Gnomad4 FIN

AF:

0.633

Gnomad4 NFE

AF:

0.576

Gnomad4 OTH

AF:

0.629

Alfa

AF:

0.591

Hom.:

19954

Bravo

AF:

0.646

TwinsUK

AF:

0.567

AC:

2101

ALSPAC

AF:

0.550

AC:

2121

ESP6500AA

AF:

0.737

AC:

3146

ESP6500EA

AF:

0.579

AC:

4869

ExAC

AF:

0.625

AC:

74635

Asia WGS

AF:

0.791

AC:

2752

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.033

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.7

PrimateAI

Benign

0.39

PROVEAN

Benign

1.9

REVEL

Benign

0.072

Sift

Benign

1.0

Sift4G

Benign

0.87

Polyphen

0.0

Vest4

0.050

MPC

0.34

ClinPred

0.011

GERP RS

3.5

Varity_R

0.066

gMVP

0.28

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