dbSNP rs3816527: PTX3:p.Ala48Asp (chr3-157437525-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

82 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PTX3	NM_002852.4 link	c.143C>A	p.Ala48Asp	missense_variant	Exon 2 of 3	ENST00000295927.4	NP_002843.2	P26022
VEPH1	NM_001167912.2 link	c.530-9037G>T		intron_variant	Intron 4 of 13	ENST00000362010.7	NP_001161384.1	Q14D04-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTX3	ENST00000295927.4 link	c.143C>A	p.Ala48Asp	missense_variant	Exon 2 of 3	1	NM_002852.4	ENSP00000295927.3		P26022
VEPH1	ENST00000362010.7 link	c.530-9037G>T		intron_variant	Intron 4 of 13	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

GnomAD2 exomes

AF:

0.636

AC:

146834

AN:

230906

AF XY:

0.633

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 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

African (AFR)

AF:

0.733

AC:

24370

AN:

33242

American (AMR)

AF:

0.700

AC:

30631

AN:

43744

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

13826

AN:

25996

East Asian (EAS)

AF:

0.823

AC:

32251

AN:

39196

South Asian (SAS)

AF:

0.699

AC:

59046

AN:

84474

European-Finnish (FIN)

AF:

0.634

AC:

32637

AN:

51498

Middle Eastern (MID)

AF:

0.578

AC:

2821

AN:

4880

European-Non Finnish (NFE)

AF:

0.567

AC:

628817

AN:

1108244

Other (OTH)

AF:

0.600

AC:

36004

AN:

59974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

20437

40874

61310

81747

102184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17662

35324

52986

70648

88310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.644

AC:

97947

AN:

152048

Hom.:

32073

Cov.:

AF XY:

0.650

AC XY:

48297

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.730

AC:

30300

AN:

41502

American (AMR)

AF:

0.672

AC:

10278

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

1889

AN:

3464

East Asian (EAS)

AF:

0.791

AC:

4065

AN:

5138

South Asian (SAS)

AF:

0.727

AC:

3508

AN:

4822

European-Finnish (FIN)

AF:

0.633

AC:

6699

AN:

10576

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.576

AC:

39121

AN:

67946

Other (OTH)

AF:

0.629

AC:

1325

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1774

3548

5321

7095

8869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.593

Hom.:

62732

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

(source)

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

PhyloP100

1.9

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over