Variant rs35948036 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002852.4(PTX3):c.46T>C(p.Leu16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,614,060 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0095 ( 9 hom., cov: 32)

Exomes 𝑓: 0.011 ( 88 hom. )

Consequence

PTX3
NM_002852.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.164

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-157436979-T-C is Benign according to our data. Variant chr3-157436979-T-C is described in ClinVar as [Benign]. Clinvar id is 770537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.164 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTX3	NM_002852.4 linkuse as main transcript	c.46T>C	p.Leu16=	synonymous_variant	1/3	ENST00000295927.4	NP_002843.2
VEPH1	NM_001167912.2 linkuse as main transcript	c.530-8491A>G		intron_variant		ENST00000362010.7	NP_001161384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTX3	ENST00000295927.4 linkuse as main transcript	c.46T>C	p.Leu16=	synonymous_variant	1/3	1	NM_002852.4	ENSP00000295927	P1
VEPH1	ENST00000362010.7 linkuse as main transcript	c.530-8491A>G		intron_variant		1	NM_001167912.2	ENSP00000354919	P1	Q14D04-1

Frequencies

GnomAD3 genomes

AF:

0.00950

AC:

1446

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00948

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0154

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00905

AC:

2275

AN:

251424

Hom.:

AF XY:

0.00904

AC XY:

1229

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00802

Gnomad ASJ exome

AF:

0.00804

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0112

AC:

16394

AN:

1461730

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

7906

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00805

Gnomad4 ASJ exome

AF:

0.00784

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.0144

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.00931

GnomAD4 genome

AF:

0.00949

AC:

1445

AN:

152330

Hom.:

Cov.:

AF XY:

0.00959

AC XY:

714

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.00947

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0154

Gnomad4 NFE

AF:

0.0142

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0122

Hom.:

Bravo

AF:

0.00863

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.0112

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.8

DANN

Benign

0.75

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