NM_002852.4:c.46T>C

Variant names:

• chr3-157436979-T-C
• rs35948036
• NM_002852.4:c.46T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002852.4(PTX3):​c.46T>C​(p.Leu16Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,614,060 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (9 hom., cov: 32)
  • Exomes 𝑓: 0.011 (88 hom.)
• Consequence: PTX3 NM_002852.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.164
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-157436979-T-C is Benign according to our data. Variant chr3-157436979-T-C is described in ClinVar as Benign. ClinVar VariationId is 770537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.164 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.46T>C	p.Leu16Leu	synonymous	Exon 1 of 3	NP_002843.2
	VEPH1	NM_001167912.2	MANE Select	c.530-8491A>G		intron	N/A	NP_001161384.1
	VEPH1	NM_024621.2		c.530-8491A>G		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.46T>C	p.Leu16Leu	synonymous	Exon 1 of 3	ENSP00000295927.3
	VEPH1	ENST00000362010.7	TSL:1 MANE Select	c.530-8491A>G		intron	N/A	ENSP00000354919.2
	VEPH1	ENST00000392833.6	TSL:1	c.530-8491A>G		intron	N/A	ENSP00000376578.2

Frequencies

GnomAD3 genomes AF: 0.00950 AC: 1446 AN: 152212 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00948

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00905 AC: 2275 AN: 251424 AF XY: 0.00904

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00802

Gnomad ASJ exome AF: 0.00804

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.0130

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0112 AC: 16394 AN: 1461730 Hom.: 88 Cov.: 30 AF XY: 0.0109 AC XY: 7906 AN XY: 727178

African (AFR) AF: 0.00170 AC: 57 AN: 33476

American (AMR) AF: 0.00805 AC: 360 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00784 AC: 205 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39692

South Asian (SAS) AF: 0.00108 AC: 93 AN: 86256

European-Finnish (FIN) AF: 0.0144 AC: 771 AN: 53408

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5766

European-Non Finnish (NFE) AF: 0.0129 AC: 14321 AN: 1111902

Other (OTH) AF: 0.00931 AC: 562 AN: 60388

GnomAD4 genome AF: 0.00949 AC: 1445 AN: 152330 Hom.: 9 Cov.: 32 AF XY: 0.00959 AC XY: 714 AN XY: 74484

African (AFR) AF: 0.00238 AC: 99 AN: 41570

American (AMR) AF: 0.00947 AC: 145 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.0154 AC: 164 AN: 10622

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0142 AC: 964 AN: 68024

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0122 Hom.: 6

Bravo AF: 0.00863

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0104

EpiControl AF: 0.0112

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.8
DANN	Benign	0.75
PhyloP100		0.16
PromoterAI		0.032	Neutral
Mutation Taster		=100/0	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: rs35948036; hg19: chr3-157154768; COSMIC: COSV55822494; COSMIC: COSV55822494;