10-3103786-C-G

Variant names:

• chr10-3103786-C-G
• NM_002627.5:c.462C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.151

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]

ACMG classification

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
PFKP	NM_002627.5	c.462C>G	p.Ile154Met	missense_variant	Exon 5 of 22	ENST00000381125.9	NP_002618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKP	ENST00000381125.9	c.462C>G	p.Ile154Met	missense_variant	Exon 5 of 22	1	NM_002627.5	ENSP00000370517.4

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

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

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;