3-157437050-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.015 (52 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (46 hom.)
• Consequence: PTX3 NM_002852.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0420

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 -14 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 id is 784028.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTX3	NM_002852.4	c.117T>G	p.His39Gln	missense_variant	1/3	ENST00000295927.4
VEPH1	NM_001167912.2	c.530-8562A>C		intron_variant		ENST00000362010.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTX3	ENST00000295927.4	c.117T>G	p.His39Gln	missense_variant	1/3	1	NM_002852.4	P1
VEPH1	ENST00000362010.7	c.530-8562A>C		intron_variant		1	NM_001167912.2	P1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2221 AN: 152170 Hom.: 52 Cov.: 32

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

GnomAD3 exomes AF: 0.00445 AC: 1119 AN: 251388 Hom.: 22 AF XY: 0.00330 AC XY: 449 AN XY: 135886

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 SAS exome AF: 0.000196

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.: 46 Cov.: 30 AF XY: 0.00176 AC XY: 1282 AN XY: 727158

Gnomad4 AFR exome AF: 0.0553

Gnomad4 AMR exome AF: 0.00394

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000431

Gnomad4 OTH exome AF: 0.00452

GnomAD4 genome AF: 0.0146 AC: 2225 AN: 152288 Hom.: 52 Cov.: 32 AF XY: 0.0143 AC XY: 1061 AN XY: 74448

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.00470

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00428 Hom.: 15

Bravo AF: 0.0166

ESP6500AA AF: 0.0479 AC: 211

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00503 AC: 611

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	11
Dann	Benign	0.80
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.031
Sift	Benign	0.37	T
Sift4G	Benign	0.45	T
Polyphen		0.0030	B
Vest4		0.096
MutPred		0.14		Loss of glycosylation at P44 (P = 0.0455);
MVP		0.13
MPC		0.23
ClinPred		0.00088	T
GERP RS		-4.0
Varity_R		0.052
gMVP		0.18

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: rs34655398; hg19: chr3-157154839;