rs3816527

chr3-157437525-C-Achr3-157437525-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002852.4(PTX3):c.143C>A(p.Ala48Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,603,296 control chromosomes in the GnomAD database, including 290,190 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.64 (32073 hom., cov: 32)
  • Exomes 𝑓: 0.59 (258117 hom.)
• Consequence: PTX3 NM_002852.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.051613E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTX3	NM_002852.4	c.143C>A	p.Ala48Asp	missense_variant	2/3	ENST00000295927.4
VEPH1	NM_001167912.2	c.530-9037G>T		intron_variant		ENST00000362010.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTX3	ENST00000295927.4	c.143C>A	p.Ala48Asp	missense_variant	2/3	1	NM_002852.4	P1
VEPH1	ENST00000362010.7	c.530-9037G>T		intron_variant		1	NM_001167912.2	P1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97822 AN: 151930 Hom.: 32017 Cov.: 32

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.621

GnomAD3 exomes AF: 0.636 AC: 146834 AN: 230906 Hom.: 47434 AF XY: 0.633 AC XY: 79940 AN XY: 126254

Gnomad AFR exome AF: 0.728

Gnomad AMR exome AF: 0.701

Gnomad ASJ exome AF: 0.529

Gnomad EAS exome AF: 0.785

Gnomad SAS exome AF: 0.698

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.599

GnomAD4 exome AF: 0.593 AC: 860403 AN: 1451248 Hom.: 258117 Cov.: 65 AF XY: 0.595 AC XY: 429357 AN XY: 721160

Gnomad4 AFR exome AF: 0.733

Gnomad4 AMR exome AF: 0.700

Gnomad4 ASJ exome AF: 0.532

Gnomad4 EAS exome AF: 0.823

Gnomad4 SAS exome AF: 0.699

Gnomad4 FIN exome AF: 0.634

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.644 AC: 97947 AN: 152048 Hom.: 32073 Cov.: 32 AF XY: 0.650 AC XY: 48297 AN XY: 74322

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.629

Alfa AF: 0.591 Hom.: 19954

Bravo AF: 0.646

TwinsUK AF: 0.567 AC: 2101

ALSPAC AF: 0.550 AC: 2121

ESP6500AA AF: 0.737 AC: 3146

ESP6500EA AF: 0.579 AC: 4869

ExAC AF: 0.625 AC: 74635

Asia WGS AF: 0.791 AC: 2752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	16
Dann	Benign	0.82
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.7	N
MutationTaster	Benign	2.6e-21	P;P;P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.072
Sift	Benign	1.0	T
Sift4G	Benign	0.87	T
Polyphen		0.0	B
Vest4		0.050
MPC		0.34
ClinPred		0.011	T
GERP RS		3.5
Varity_R		0.066
gMVP		0.28

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

Other links and lift over

dbSNP: rs3816527; hg19: chr3-157155314; COSMIC: COSV55821899; COSMIC: COSV55821899;