rs17132175

Positions:

• chr10-3108622-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002627.5(PFKP):​c.871-79G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 1,034,094 control chromosomes in the GnomAD database, including 4,902 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 0.095 (746 hom., cov: 33)
  • Exomes 𝑓: 0.092 (4156 hom.)
• Consequence: PFKP NM_002627.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKP	NM_002627.5	c.871-79G>C		intron_variant		ENST00000381125.9	NP_002618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFKP	ENST00000381125.9	c.871-79G>C		intron_variant		1	NM_002627.5	ENSP00000370517.4

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14368 AN: 152064 Hom.: 743 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0935

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.00750

Gnomad SAS AF: 0.0430

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.0840

GnomAD4 exome AF: 0.0924 AC: 81451 AN: 881912 Hom.: 4156 AF XY: 0.0898 AC XY: 40912 AN XY: 455680

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.0881

Gnomad4 ASJ exome AF: 0.0715

Gnomad4 EAS exome AF: 0.00293

Gnomad4 SAS exome AF: 0.0468

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0870

GnomAD4 genome AF: 0.0945 AC: 14382 AN: 152182 Hom.: 746 Cov.: 33 AF XY: 0.0945 AC XY: 7029 AN XY: 74420

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0935

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.00771

Gnomad4 SAS AF: 0.0426

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0974

Gnomad4 OTH AF: 0.0836

Alfa AF: 0.0945 Hom.: 95

Bravo AF: 0.0934

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.58
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs17132175; hg19: chr10-3150814; COSMIC: COSV66898745; COSMIC: COSV66898745;