4-73981902-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000296029.4(PF4):​c.52G>A​(p.Gly18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PF4
ENST00000296029.4 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.542
Variant links:
Genes affected
PF4 (HGNC:8861): (platelet factor 4) This gene encodes a member of the CXC chemokine family. This chemokine is released from the alpha granules of activated platelets in the form of a homotetramer which has high affinity for heparin and is involved in platelet aggregation. This protein is chemotactic for numerous other cell type and also functions as an inhibitor of hematopoiesis, angiogenesis and T-cell function. The protein also exhibits antimicrobial activity against Plasmodium falciparum. [provided by RefSeq, Oct 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PF4NM_002619.4 linkuse as main transcriptc.52G>A p.Gly18Arg missense_variant 1/3 ENST00000296029.4 NP_002610.1
PF4NM_001363352.1 linkuse as main transcriptc.-127G>A 5_prime_UTR_variant 1/3 NP_001350281.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PF4ENST00000296029.4 linkuse as main transcriptc.52G>A p.Gly18Arg missense_variant 1/31 NM_002619.4 ENSP00000296029 P1
PF4ENST00000687529.1 linkuse as main transcriptc.52G>A p.Gly18Arg missense_variant, NMD_transcript_variant 1/3 ENSP00000508485

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1399184
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
690104
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
28

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 01, 2023The c.52G>A (p.G18R) alteration is located in exon 1 (coding exon 1) of the PF4 gene. This alteration results from a G to A substitution at nucleotide position 52, causing the glycine (G) at amino acid position 18 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.69
BayesDel_addAF
Uncertain
0.088
D
BayesDel_noAF
Benign
-0.11
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.49
T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0018
T
MetaRNN
Pathogenic
0.79
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.97
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.21
Sift
Benign
0.035
D
Sift4G
Uncertain
0.060
T
Polyphen
1.0
D
Vest4
0.54
MutPred
0.75
Gain of methylation at G18 (P = 0.0282);
MVP
0.72
MPC
0.15
ClinPred
0.63
D
GERP RS
1.2
Varity_R
0.087
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1433634007; hg19: chr4-74847619; API