10-3103786-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001323069.2(PFKP):​c.-46C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PFKP
NM_001323069.2 5_prime_UTR_premature_start_codon_gain

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.151
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PFKPNM_002627.5 linkc.462C>G p.Ile154Met missense_variant Exon 5 of 22 ENST00000381125.9 NP_002618.1 Q01813-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PFKPENST00000381125.9 linkc.462C>G p.Ile154Met missense_variant Exon 5 of 22 1 NM_002627.5 ENSP00000370517.4 Q01813-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461538
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727074
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.462C>G (p.I154M) alteration is located in exon 5 (coding exon 5) of the PFKP gene. This alteration results from a C to G substitution at nucleotide position 462, causing the isoleucine (I) at amino acid position 154 to be replaced by a methionine (M). 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
0.068
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.85
D;.;D
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.51
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.94
D;D;D
MetaSVM
Uncertain
0.12
D
MutationAssessor
Pathogenic
4.2
H;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-2.8
D;D;D
REVEL
Uncertain
0.51
Sift
Uncertain
0.010
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
0.61
P;.;.
Vest4
0.78
MutPred
0.81
Gain of disorder (P = 0.0428);.;.;
MVP
0.69
MPC
0.64
ClinPred
0.99
D
GERP RS
-1.3
Varity_R
0.68
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.19
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-3145978; API