chr3-157443210-C-T

Variant names:

• chr3-157443210-C-T
• rs2614
• NM_002852.4:c.*231C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002852.4(PTX3):​c.*231C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 458,640 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.031 (276 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (54 hom.)
• Consequence: PTX3 NM_002852.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 9 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTX3	NM_002852.4	MANE Select	c.*231C>T		3_prime_UTR	Exon 3 of 3	NP_002843.2
	VEPH1	NM_001167912.2	MANE Select	c.530-14722G>A		intron	N/A	NP_001161384.1
	VEPH1	NM_024621.2		c.530-14722G>A		intron	N/A	NP_078897.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTX3	ENST00000295927.4	TSL:1 MANE Select	c.*231C>T		3_prime_UTR	Exon 3 of 3	ENSP00000295927.3
	VEPH1	ENST00000362010.7	TSL:1 MANE Select	c.530-14722G>A		intron	N/A	ENSP00000354919.2
	VEPH1	ENST00000392833.6	TSL:1	c.530-14722G>A		intron	N/A	ENSP00000376578.2

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4686 AN: 152162 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00910

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00543 AC: 1663 AN: 306360 Hom.: 54 Cov.: 4 AF XY: 0.00488 AC XY: 766 AN XY: 157064

African (AFR) AF: 0.101 AC: 1030 AN: 10168

American (AMR) AF: 0.00705 AC: 79 AN: 11198

Ashkenazi Jewish (ASJ) AF: 0.000389 AC: 4 AN: 10292

East Asian (EAS) AF: 0.0119 AC: 302 AN: 25378

South Asian (SAS) AF: 0.000221 AC: 3 AN: 13548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20350

Middle Eastern (MID) AF: 0.00479 AC: 7 AN: 1462

European-Non Finnish (NFE) AF: 0.000374 AC: 73 AN: 194992

Other (OTH) AF: 0.00870 AC: 165 AN: 18972

GnomAD4 genome AF: 0.0308 AC: 4692 AN: 152280 Hom.: 276 Cov.: 32 AF XY: 0.0298 AC XY: 2219 AN XY: 74462

African (AFR) AF: 0.107 AC: 4456 AN: 41546

American (AMR) AF: 0.00902 AC: 138 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00425 AC: 22 AN: 5180

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68022

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.0168 Hom.: 37

Bravo AF: 0.0346

Asia WGS AF: 0.00808 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2614; hg19: chr3-157160999;