chr3-157437762-C-A

Variant names:

• chr3-157437762-C-A
• rs1197955708
• NM_002852.4:c.380C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002852.4(PTX3):​c.380C>A​(p.Ala127Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000202 in 1,486,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: PTX3 NM_002852.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052648216).

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.380C>A	p.Ala127Glu	missense	Exon 2 of 3	NP_002843.2	P26022
	VEPH1	NM_001167912.2	MANE Select	c.530-9274G>T		intron	N/A	NP_001161384.1	Q14D04-1
	VEPH1	NM_024621.2		c.530-9274G>T		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.380C>A	p.Ala127Glu	missense	Exon 2 of 3	ENSP00000295927.3	P26022
	VEPH1	ENST00000362010.7	TSL:1 MANE Select	c.530-9274G>T		intron	N/A	ENSP00000354919.2	Q14D04-1
	VEPH1	ENST00000392833.6	TSL:1	c.530-9274G>T		intron	N/A	ENSP00000376578.2	Q14D04-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1334866 Hom.: 0 Cov.: 35 AF XY: 0.00000152 AC XY: 1 AN XY: 657990

African (AFR) AF: 0.00 AC: 0 AN: 26466

American (AMR) AF: 0.00 AC: 0 AN: 27378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22672

East Asian (EAS) AF: 0.00 AC: 0 AN: 31102

South Asian (SAS) AF: 0.00 AC: 0 AN: 73300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3906

European-Non Finnish (NFE) AF: 9.43e-7 AC: 1 AN: 1060910

Other (OTH) AF: 0.00 AC: 0 AN: 55492

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152078 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74276

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.3
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	1.2	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	0.45	T
Polyphen		0.0040	B
Vest4		0.16
MutPred		0.26		Gain of loop (P = 0.0045)
MVP		0.17
MPC		0.27
ClinPred		0.066	T
GERP RS		0.36
Varity_R		0.13
gMVP		0.44
Mutation Taster		=94/6	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: rs1197955708; hg19: chr3-157155551;