dbSNP rs765704070: PF4:p.Gly64Arg (chr4-73981445-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_002619.4(PF4):c.190G>C(p.Gly64Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

PF4
NM_002619.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.155

Publications

0 publications found

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]

PF4 links:

ENSG00000288796 (HGNC:):

ENSG00000288796 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.774

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002619.4. 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
	PF4	NM_002619.4	MANE Select	c.190G>C	p.Gly64Arg	missense	Exon 2 of 3	NP_002610.1	P02776
	PF4	NM_001363352.1		c.217G>C	p.Gly73Arg	missense	Exon 2 of 3	NP_001350281.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PF4	ENST00000296029.4	TSL:1 MANE Select	c.190G>C	p.Gly64Arg	missense	Exon 2 of 3	ENSP00000296029.3	P02776
ENSG00000288796	ENST00000693342.1		c.466G>C	p.Gly156Arg	missense	Exon 4 of 5	ENSP00000510492.1	A0A8I5KW61
PF4	ENST00000687529.1		n.*221G>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000508485.1	A0A8I5QJ57

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251378

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

Eigen

Benign

0.034

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0051

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

0.15

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-7.8

REVEL

Benign

0.089

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.31

MutPred

0.79

Gain of solvent accessibility (P = 0.0037)

MVP

0.65

MPC

0.54

ClinPred

0.95

GERP RS

2.6

Varity_R

0.76

gMVP

0.47

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: 13

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over