dbSNP rs1401039990: PFKP:p.Ser6Tyr (chr10-3067612-C-A) – 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.17C>A(p.Ser6Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000785 in 1,529,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. S6F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

PFKP
NM_002627.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.986

Publications

1 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:

Genome browser will be placed here

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=0.20548692).

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.17C>A	p.Ser6Tyr	missense	Exon 1 of 22	NP_002618.1	Q01813-1
PFKP	NM_001410880.1		c.17C>A	p.Ser6Tyr	missense	Exon 1 of 23	NP_001397809.1	A0A8V8TMY4
PFKP	NM_001323068.2		c.17C>A	p.Ser6Tyr	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.17C>A	p.Ser6Tyr	missense	Exon 1 of 22	ENSP00000370517.4	Q01813-1
PFKP	ENST00000699222.1		c.17C>A	p.Ser6Tyr	missense	Exon 1 of 23	ENSP00000514216.1	A0A8V8TMY4
PFKP	ENST00000963518.1		c.17C>A	p.Ser6Tyr	missense	Exon 1 of 22	ENSP00000633577.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

122854

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000799

AC:

AN:

1377276

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

679582

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29126

American (AMR)

AF:

0.00

AC:

AN:

34698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24494

East Asian (EAS)

AF:

0.00

AC:

AN:

32694

South Asian (SAS)

AF:

0.00

AC:

AN:

77924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45964

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.00000935

AC:

AN:

1069588

Other (OTH)

AF:

0.0000175

AC:

AN:

57188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

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

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.17

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.49

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.34

PhyloP100

0.99

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.52

REVEL

Benign

0.19

Sift

Benign

0.033

Sift4G

Uncertain

0.012

Polyphen

0.45

Vest4

0.20

MutPred

0.29

Loss of disorder (P = 0.025)

MVP

0.40

MPC

0.25

ClinPred

0.13

GERP RS

3.2

PromoterAI

0.053

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.064

gMVP

0.47

Mutation Taster

=100/0

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