dbSNP rs2614: PTX3:c.*231C>T (chr3-157443210-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_002852.4(PTX3):c.*231C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 458,640 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 276 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 54 hom. )

Consequence

PTX3
NM_002852.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.14

Publications

9 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTX3	NM_002852.4 link	c.*231C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000295927.4	NP_002843.2
VEPH1	NM_001167912.2 link	c.530-14722G>A		intron_variant	Intron 4 of 13	ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTX3	ENST00000295927.4 link	c.*231C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_002852.4	ENSP00000295927.3
VEPH1	ENST00000362010.7 link	c.530-14722G>A		intron_variant	Intron 4 of 13	1	NM_001167912.2	ENSP00000354919.2

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4686

AN:

152162

Hom.:

274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00910

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0163

GnomAD4 exome

AF:

0.00543

AC:

1663

AN:

306360

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

766

AN XY:

157064

show subpopulations

African (AFR)

AF:

0.101

AC:

1030

AN:

10168

American (AMR)

AF:

0.00705

AC:

AN:

11198

Ashkenazi Jewish (ASJ)

AF:

0.000389

AC:

AN:

10292

East Asian (EAS)

AF:

0.0119

AC:

302

AN:

25378

South Asian (SAS)

AF:

0.000221

AC:

AN:

13548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20350

Middle Eastern (MID)

AF:

0.00479

AC:

AN:

1462

European-Non Finnish (NFE)

AF:

0.000374

AC:

AN:

194992

Other (OTH)

AF:

0.00870

AC:

165

AN:

18972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

140

210

280

350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0308

AC:

4692

AN:

152280

Hom.:

276

Cov.:

AF XY:

0.0298

AC XY:

2219

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.107

AC:

4456

AN:

41546

American (AMR)

AF:

0.00902

AC:

138

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00425

AC:

AN:

5180

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68022

Other (OTH)

AF:

0.0161

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

197

394

591

788

985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0168

Hom.:

Bravo

AF:

0.0346

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

2.1

Mutation Taster

=100/0

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