Genetic Variant NM_002627.5:c.1197C>G (chr10-3113161-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002627.5(PFKP):c.1197C>G(p.Ile399Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PFKP
NM_002627.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.357

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22562388).

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
PFKP	NM_002627.5	MANE Select	c.1197C>G	p.Ile399Met	missense	Exon 12 of 22	NP_002618.1
PFKP	NM_001410880.1		c.1197C>G	p.Ile399Met	missense	Exon 12 of 23	NP_001397809.1
PFKP	NM_001242339.2		c.1173C>G	p.Ile391Met	missense	Exon 14 of 24	NP_001229268.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PFKP	ENST00000381125.9	TSL:1 MANE Select	c.1197C>G	p.Ile399Met	missense	Exon 12 of 22	ENSP00000370517.4
PFKP	ENST00000699222.1		c.1197C>G	p.Ile399Met	missense	Exon 12 of 23	ENSP00000514216.1
PFKP	ENST00000381075.7	TSL:2	c.1083C>G	p.Ile361Met	missense	Exon 13 of 23	ENSP00000370465.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460220

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111346

Other (OTH)

AF:

0.0000332

AC:

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

0.091

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.17

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.63

M_CAP

Benign

0.058

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.59

MutationAssessor

Benign

-0.55

PhyloP100

-0.36

PrimateAI

Benign

0.34

PROVEAN

Benign

0.58

REVEL

Benign

0.29

Sift

Benign

0.22

Sift4G

Benign

0.26

Polyphen

0.63

Vest4

0.23

MutPred

0.75

Gain of ubiquitination at K400 (P = 0.0773)

MVP

0.60

MPC

0.20

ClinPred

0.14

GERP RS

-0.66

PromoterAI

0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.067

gMVP

0.51

Mutation Taster

=90/10

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