4-73981916-C-T

Variant names:

• chr4-73981916-C-T
• NM_002619.4:c.38G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002619.4(PF4):​c.38G>A​(p.Gly13Glu) 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 benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: PF4 NM_002619.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0400

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]

ENSG00000288796 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13265333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PF4	NM_002619.4	c.38G>A	p.Gly13Glu	missense_variant	Exon 1 of 3	ENST00000296029.4	NP_002610.1
PF4	NM_001363352.1	c.-141G>A		5_prime_UTR_variant	Exon 1 of 3		NP_001350281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PF4	ENST00000296029.4	c.38G>A	p.Gly13Glu	missense_variant	Exon 1 of 3	1	NM_002619.4	ENSP00000296029.3
ENSG00000288796	ENST00000693342.1	c.368-373G>A		intron_variant	Intron 3 of 4			ENSP00000510492.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.38G>A (p.G13E) 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 38, causing the glycine (G) at amino acid position 13 to be replaced by a glutamic acid (E). 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	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.72
DANN	Benign	0.85
DEOGEN2	Benign	0.30	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.00075	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.11	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.028
Sift	Benign	0.69	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.091
MutPred		0.44		Loss of glycosylation at P12 (P = 0.0865);
MVP		0.37
MPC		0.12
ClinPred		0.051	T
GERP RS		0.27
Varity_R		0.066
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-74847633;