3-157437882-A-G

Position:

chr3-157437882-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002852.4(PTX3):c.500A>G(p.Gln167Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00724 in 1,514,912 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 15 hom., cov: 31)

Exomes 𝑓: 0.0070 ( 92 hom. )

Consequence

PTX3
NM_002852.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0500

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020294487).

BP6

Variant 3-157437882-A-G is Benign according to our data. Variant chr3-157437882-A-G is described in ClinVar as [Benign]. Clinvar id is 770895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00902 (1372/152098) while in subpopulation AMR AF= 0.0331 (506/15288). AF 95% confidence interval is 0.0307. There are 15 homozygotes in gnomad4. There are 770 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTX3	NM_002852.4 link	c.500A>G	p.Gln167Arg	missense_variant	2/3	ENST00000295927.4	NP_002843.2	P26022
VEPH1	NM_001167912.2 link	c.530-9394T>C		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 link	c.500A>G	p.Gln167Arg	missense_variant	2/3	1	NM_002852.4	ENSP00000295927.3		P26022
VEPH1	ENST00000362010.7 link	c.530-9394T>C		intron_variant		1	NM_001167912.2	ENSP00000354919.2		Q14D04-1

Frequencies

GnomAD3 genomes

AF:

0.00905

AC:

1376

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0332

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00332

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0302

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00617

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.0167

AC:

1840

AN:

109912

Hom.:

AF XY:

0.0132

AC XY:

812

AN XY:

61748

show subpopulations

Gnomad AFR exome

AF:

0.000303

Gnomad AMR exome

AF:

0.0612

Gnomad ASJ exome

AF:

0.00163

Gnomad EAS exome

AF:

0.00352

Gnomad SAS exome

AF:

0.00152

Gnomad FIN exome

AF:

0.0318

Gnomad NFE exome

AF:

0.00629

Gnomad OTH exome

AF:

0.0151

GnomAD4 exome

AF:

0.00705

AC:

9602

AN:

1362814

Hom.:

Cov.:

AF XY:

0.00669

AC XY:

4503

AN XY:

673120

show subpopulations

Gnomad4 AFR exome

AF:

0.000833

Gnomad4 AMR exome

AF:

0.0520

Gnomad4 ASJ exome

AF:

0.00192

Gnomad4 EAS exome

AF:

0.00485

Gnomad4 SAS exome

AF:

0.00144

Gnomad4 FIN exome

AF:

0.0287

Gnomad4 NFE exome

AF:

0.00574

Gnomad4 OTH exome

AF:

0.00700

GnomAD4 genome

AF:

0.00902

AC:

1372

AN:

152098

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

770

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.0331

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00333

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.0302

Gnomad4 NFE

AF:

0.00617

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00721

Hom.:

Bravo

AF:

0.00900

ESP6500AA

AF:

0.000512

AC:

ESP6500EA

AF:

0.00312

AC:

ExAC

AF:

0.00735

AC:

698

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.84

DANN

Benign

0.49

DEOGEN2

Benign

0.10

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.1

REVEL

Benign

0.026

Sift

Benign

0.10

Sift4G

Benign

0.70

Polyphen

0.0030

Vest4

0.056

MPC

0.25

ClinPred

0.0011

GERP RS

-2.6

Varity_R

0.052

gMVP

0.44

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