3-157437040-A-C

Variant names:

• chr3-157437040-A-C
• NM_002852.4:c.107A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002852.4(PTX3):​c.107A>C​(p.Asn36Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 (★). Synonymous variant affecting the same amino acid position (i.e. N36N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTX3 NM_002852.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12461206).

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.107A>C	p.Asn36Thr	missense	Exon 1 of 3	NP_002843.2	P26022
	VEPH1	NM_001167912.2	MANE Select	c.530-8552T>G		intron	N/A	NP_001161384.1	Q14D04-1
	VEPH1	NM_024621.2		c.530-8552T>G		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.107A>C	p.Asn36Thr	missense	Exon 1 of 3	ENSP00000295927.3	P26022
	VEPH1	ENST00000362010.7	TSL:1 MANE Select	c.530-8552T>G		intron	N/A	ENSP00000354919.2	Q14D04-1
	VEPH1	ENST00000392833.6	TSL:1	c.530-8552T>G		intron	N/A	ENSP00000376578.2	Q14D04-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461534 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727058

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111738

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

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	-0.61
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.0
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.091
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.042	D
Polyphen		0.36	B
Vest4		0.22
MutPred		0.27		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.36
MPC		0.33
ClinPred		0.44	T
GERP RS		2.5
PromoterAI		-0.016	Neutral
Varity_R		0.086
gMVP		0.16
Mutation Taster		=82/18	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

hg19: chr3-157154829;