3-157437050-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002852.4(PTX3):c.117T>G(p.His39Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,613,962 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 52 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 46 hom. )

Consequence

PTX3
NM_002852.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0420

Publications

8 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017979145).

BP6

Variant 3-157437050-T-G is Benign according to our data. Variant chr3-157437050-T-G is described in ClinVar as Benign. ClinVar VariationId is 784028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0532 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002852.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTX3	NM_002852.4	MANE Select	c.117T>G	p.His39Gln	missense	Exon 1 of 3	NP_002843.2	P26022
VEPH1	NM_001167912.2	MANE Select	c.530-8562A>C		intron	N/A	NP_001161384.1	Q14D04-1
VEPH1	NM_024621.2		c.530-8562A>C		intron	N/A	NP_078897.2	Q14D04-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTX3	ENST00000295927.4	TSL:1 MANE Select	c.117T>G	p.His39Gln	missense	Exon 1 of 3	ENSP00000295927.3	P26022
VEPH1	ENST00000362010.7	TSL:1 MANE Select	c.530-8562A>C		intron	N/A	ENSP00000354919.2	Q14D04-1
VEPH1	ENST00000392833.6	TSL:1	c.530-8562A>C		intron	N/A	ENSP00000376578.2	Q14D04-2

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2221

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00445

AC:

1119

AN:

251388

AF XY:

0.00330

show subpopulations

Gnomad AFR exome

AF:

0.0552

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00199

AC:

2902

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1282

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.0553

AC:

1851

AN:

33476

American (AMR)

AF:

0.00394

AC:

176

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00214

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000232

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00815

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000431

AC:

479

AN:

1111854

Other (OTH)

AF:

0.00452

AC:

273

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

151

302

454

605

756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<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:

0.0146

AC:

2225

AN:

152288

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1061

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0503

AC:

2090

AN:

41544

American (AMR)

AF:

0.00470

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68030

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

106

212

319

425

531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00785

Hom.:

Bravo

AF:

0.0166

ESP6500AA

AF:

0.0479

AC:

211

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00503

AC:

611

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.039

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

PhyloP100

-0.042

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.050

REVEL

Benign

0.031

Sift

Benign

0.37

Sift4G

Benign

0.45

Polyphen

0.0030

Vest4

0.096

MutPred

0.14

Loss of glycosylation at P44 (P = 0.0455)

MVP

0.13

MPC

0.23

ClinPred

0.00088

GERP RS

-4.0

PromoterAI

0.060

Neutral

(source)

Varity_R

0.052

gMVP

0.18

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over