Genetic Variant PFKP:p.Ser6Phe (chr10-3067612-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_002627.5(PFKP):c.17C>T(p.Ser6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000726 in 1,377,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

PFKP
NM_002627.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.986

Variant links:

Genes affected

PFKP (HGNC:8878): (phosphofructokinase, platelet) This gene encodes a member of the phosphofructokinase A protein family. The encoded enzyme is the platelet-specific isoform of phosphofructokinase and plays a key role in glycolysis regulation. This gene may play a role in metabolic reprogramming in some cancers, including clear cell renal cell carcinomas, and cancer of the bladder, breast, and lung. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

PFKP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity PFKAP_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17791253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFKP	NM_002627.5 link	c.17C>T	p.Ser6Phe	missense_variant	Exon 1 of 22	ENST00000381125.9	NP_002618.1	Q01813-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PFKP	ENST00000381125.9 link	c.17C>T	p.Ser6Phe	missense_variant	Exon 1 of 22	1	NM_002627.5	ENSP00000370517.4	Q01813-1
PFKP	ENST00000699222.1 link	c.17C>T	p.Ser6Phe	missense_variant	Exon 1 of 23			ENSP00000514216.1	A0A8V8TMY4
PFKP	ENST00000607886.5 link	c.-3+1190C>T		intron_variant	Intron 1 of 3	5		ENSP00000477128.1	V9GYV7
PFKP	ENST00000495715.1 link	n.-60C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000814

AC:

AN:

122854

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000232

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000726

AC:

AN:

1377278

Hom.:

Cov.:

AF XY:

0.0000118

AC XY:

AN XY:

679582

show subpopulations

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:

0.00000841

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000435

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.17C>T (p.S6F) alteration is located in exon 1 (coding exon 1) of the PFKP gene. This alteration results from a C to T substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 to be replaced by a phenylalanine (F). 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

0.097

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.17

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.79

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.34

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.54

REVEL

Benign

0.18

Sift

Benign

0.038

Sift4G

Uncertain

0.011

Polyphen

0.12

Vest4

0.14

MVP

0.36

MPC

0.21

ClinPred

0.10

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.058

gMVP

0.50

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over