Genetic Variant NM_002627.5:c.22G>T (chr10-3067617-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002627.5(PFKP):c.22G>T(p.Ala8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,377,412 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A8P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PFKP
NM_002627.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

0 publications found

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:

PFKP-DT (HGNC:55177): (PFKP divergent transcript)

PFKP-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066385776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002627.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PFKP	NM_002627.5	MANE Select	c.22G>T	p.Ala8Ser	missense	Exon 1 of 22	NP_002618.1	Q01813-1
PFKP	NM_001410880.1		c.22G>T	p.Ala8Ser	missense	Exon 1 of 23	NP_001397809.1	A0A8V8TMY4
PFKP	NM_001323068.2		c.22G>T	p.Ala8Ser	missense	Exon 1 of 21	NP_001309997.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PFKP	ENST00000381125.9	TSL:1 MANE Select	c.22G>T	p.Ala8Ser	missense	Exon 1 of 22	ENSP00000370517.4	Q01813-1
PFKP	ENST00000699222.1		c.22G>T	p.Ala8Ser	missense	Exon 1 of 23	ENSP00000514216.1	A0A8V8TMY4
PFKP	ENST00000963518.1		c.22G>T	p.Ala8Ser	missense	Exon 1 of 22	ENSP00000633577.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1377412

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

679628

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29138

American (AMR)

AF:

0.00

AC:

AN:

34718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24486

East Asian (EAS)

AF:

0.00

AC:

AN:

32716

South Asian (SAS)

AF:

0.00

AC:

AN:

77950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1069560

Other (OTH)

AF:

0.00

AC:

AN:

57188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.55

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.15

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.34

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.69

PhyloP100

-0.058

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.12

REVEL

Benign

0.095

Sift

Benign

0.60

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.061

MutPred

0.20

Gain of phosphorylation at A8 (P = 0.0051)

MVP

0.22

MPC

0.17

ClinPred

0.018

GERP RS

-3.6

PromoterAI

-0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.027

gMVP

0.14

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over