rs143287219

Variant names:

• chr3-157442752-A-G
• rs143287219
• NM_002852.4:c.919A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002852.4(PTX3):​c.919A>G​(p.Ile307Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 1,614,096 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (1 hom.)
• Consequence: PTX3 NM_002852.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• Publications: 1 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09119043).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTX3	NM_002852.4	MANE Select	c.919A>G	p.Ile307Val	missense	Exon 3 of 3	NP_002843.2	P26022
	VEPH1	NM_001167912.2	MANE Select	c.530-14264T>C		intron	N/A	NP_001161384.1	Q14D04-1
	VEPH1	NM_024621.2		c.530-14264T>C		intron	N/A	NP_078897.2	Q14D04-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTX3	ENST00000295927.4	TSL:1 MANE Select	c.919A>G	p.Ile307Val	missense	Exon 3 of 3	ENSP00000295927.3	P26022
	VEPH1	ENST00000362010.7	TSL:1 MANE Select	c.530-14264T>C		intron	N/A	ENSP00000354919.2	Q14D04-1
	VEPH1	ENST00000392833.6	TSL:1	c.530-14264T>C		intron	N/A	ENSP00000376578.2	Q14D04-2

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000274 AC: 69 AN: 251494 AF XY: 0.000243

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000563

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000465 AC: 680 AN: 1461892 Hom.: 1 Cov.: 31 AF XY: 0.000436 AC XY: 317 AN XY: 727246

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000599 AC: 666 AN: 1112010

Other (OTH) AF: 0.000149 AC: 9 AN: 60396

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74360

African (AFR) AF: 0.000169 AC: 7 AN: 41454

American (AMR) AF: 0.000196 AC: 3 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000474 Hom.: 0

Bravo AF: 0.000242

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000198 AC: 24

EpiCase AF: 0.000327

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.5
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.091
Sift	Benign	0.17	T
Sift4G	Benign	0.31	T
Polyphen		0.55	P
Vest4		0.079
MVP		0.38
MPC		0.26
ClinPred		0.030	T
GERP RS		0.79
Varity_R		0.060
gMVP		0.59
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs143287219; hg19: chr3-157160541;