Genetic Variant PFKP:p.Ile399Ile (chr10-3113161-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002627.5(PFKP):c.1197C>T(p.Ile399Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,612,188 control chromosomes in the GnomAD database, including 18,807 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1954 hom., cov: 35)

Exomes 𝑓: 0.15 ( 16853 hom. )

Consequence

PFKP
NM_002627.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.357

Publications

18 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP7

Synonymous conserved (PhyloP=-0.357 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFKP	NM_002627.5 link	c.1197C>T	p.Ile399Ile	synonymous_variant	Exon 12 of 22	ENST00000381125.9	NP_002618.1	Q01813-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKP	ENST00000381125.9 link	c.1197C>T	p.Ile399Ile	synonymous_variant	Exon 12 of 22	1	NM_002627.5	ENSP00000370517.4		Q01813-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23382

AN:

152182

Hom.:

1951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.0613

Gnomad SAS

AF:

0.0682

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.156

GnomAD2 exomes

AF:

0.149

AC:

37098

AN:

248152

AF XY:

0.145

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.224

Gnomad EAS exome

AF:

0.0655

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.149

AC:

217406

AN:

1459888

Hom.:

16853

Cov.:

AF XY:

0.146

AC XY:

106324

AN XY:

726082

show subpopulations

African (AFR)

AF:

0.160

AC:

5366

AN:

33450

American (AMR)

AF:

0.205

AC:

9134

AN:

44468

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

5842

AN:

26116

East Asian (EAS)

AF:

0.0745

AC:

2954

AN:

39654

South Asian (SAS)

AF:

0.0719

AC:

6181

AN:

85986

European-Finnish (FIN)

AF:

0.159

AC:

8410

AN:

53000

Middle Eastern (MID)

AF:

0.158

AC:

910

AN:

5766

European-Non Finnish (NFE)

AF:

0.153

AC:

169575

AN:

1111134

Other (OTH)

AF:

0.150

AC:

9034

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

9293

18587

27880

37174

46467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6024

12048

18072

24096

30120

<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

AF:

0.154

AC:

23398

AN:

152300

Hom.:

1954

Cov.:

AF XY:

0.150

AC XY:

11193

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.150

AC:

6249

AN:

41576

American (AMR)

AF:

0.179

AC:

2744

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

809

AN:

3470

East Asian (EAS)

AF:

0.0608

AC:

315

AN:

5178

South Asian (SAS)

AF:

0.0674

AC:

326

AN:

4834

European-Finnish (FIN)

AF:

0.149

AC:

1581

AN:

10616

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10819

AN:

68006

Other (OTH)

AF:

0.155

AC:

327

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1030

2059

3089

4118

5148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.161

Hom.:

4232

Bravo

AF:

0.161

Asia WGS

AF:

0.0830

AC:

288

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.4

(source)

DANN

Benign

0.76

PhyloP100

-0.36

PromoterAI

-0.069

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over