10-3101404-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001323069.2(PFKP):​c.-199C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000512 in 1,602,134 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: 𝑓 0.000079 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

PFKP
NM_001323069.2 5_prime_UTR_premature_start_codon_gain

Scores

5
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PFKPNM_002627.5 linkc.304C>T p.Arg102Cys missense_variant Exon 4 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.304C>T p.Arg102Cys missense_variant Exon 4 of 22 1 NM_002627.5 ENSP00000370517.4 Q01813-1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152200
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.0000973
AC:
22
AN:
226082
Hom.:
0
AF XY:
0.0000732
AC XY:
9
AN XY:
122954
show subpopulations
Gnomad AFR exome
AF:
0.0000729
Gnomad AMR exome
AF:
0.0000924
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000119
Gnomad SAS exome
AF:
0.0000704
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000139
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000483
AC:
70
AN:
1449816
Hom.:
0
Cov.:
31
AF XY:
0.0000472
AC XY:
34
AN XY:
720330
show subpopulations
Gnomad4 AFR exome
AF:
0.0000903
Gnomad4 AMR exome
AF:
0.000139
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000256
Gnomad4 SAS exome
AF:
0.0000593
Gnomad4 FIN exome
AF:
0.0000191
Gnomad4 NFE exome
AF:
0.0000443
Gnomad4 OTH exome
AF:
0.0000669
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152318
Hom.:
0
Cov.:
31
AF XY:
0.000107
AC XY:
8
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.0000279
Hom.:
0
Bravo
AF:
0.0000756
ExAC
AF:
0.000157
AC:
19

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.304C>T (p.R102C) alteration is located in exon 4 (coding exon 4) of the PFKP gene. This alteration results from a C to T substitution at nucleotide position 304, causing the arginine (R) at amino acid position 102 to be replaced by a cysteine (C). 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
0.18
BayesDel_addAF
Uncertain
0.090
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.89
.;D;.;D
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Uncertain
0.21
D
MetaRNN
Pathogenic
0.83
D;D;D;D
MetaSVM
Uncertain
0.70
D
MutationAssessor
Pathogenic
3.9
.;H;.;.
PrimateAI
Benign
0.47
T
PROVEAN
Pathogenic
-6.3
.;D;D;D
REVEL
Uncertain
0.61
Sift
Uncertain
0.0030
.;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.78, 0.80
MVP
0.79
MPC
0.83
ClinPred
0.97
D
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.77
gMVP
0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138939047; hg19: chr10-3143596; API