chr4-73987334-C-T

Variant names:

• chr4-73987334-C-T
• rs1446904093
• NM_002704.3:c.325G>A

Variant summary

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

The NM_002704.3(PPBP):​c.325G>A​(p.Asp109Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PPBP NM_002704.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.667
• Publications: 0 publications found

Genes affected

PPBP (HGNC:9240): (pro-platelet basic protein) The protein encoded by this gene is a platelet-derived growth factor that belongs to the CXC chemokine family. This growth factor is a potent chemoattractant and activator of neutrophils. It has been shown to stimulate various cellular processes including DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates the formation and secretion of plasminogen activator by synovial cells. The protein also is an antimicrobial protein with bactericidal and antifungal activity. [provided by RefSeq, Nov 2014]

ENSG00000288796 (HGNC:):

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=0.0835067).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002704.3. 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
	PPBP	NM_002704.3	MANE Select	c.325G>A	p.Asp109Asn	missense	Exon 3 of 3	NP_002695.1	P02775

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPBP	ENST00000296028.4	TSL:1 MANE Select	c.325G>A	p.Asp109Asn	missense	Exon 3 of 3	ENSP00000296028.3	P02775
	ENSG00000288796	ENST00000693342.1		c.325G>A	p.Asp109Asn	missense	Exon 3 of 5	ENSP00000510492.1	A0A8I5KW61
	PPBP	ENST00000716905.1		c.325G>A	p.Asp109Asn	missense	Exon 3 of 3	ENSP00000520613.1	P02775

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251430 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461752 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111904

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.000111 Hom.: 0

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	0.076
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.44	N
PhyloP100		0.67
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.023
Sift	Benign	0.17	T
Sift4G	Benign	0.13	T
Polyphen		0.0090	B
Vest4		0.21
MutPred		0.37		Gain of catalytic residue at D109 (P = 0.0088)
MVP		0.22
MPC		0.017
ClinPred		0.089	T
GERP RS		0.92
Varity_R		0.25
gMVP		0.11
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1446904093; hg19: chr4-74853051;