NM_002627.5:c.186+4992C>T

Variant names:

• chr10-3087453-C-T
• rs9630129
• NM_002627.5:c.186+4992C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002627.5(PFKP):​c.186+4992C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,070 control chromosomes in the GnomAD database, including 16,580 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 0.46 (16580 hom., cov: 32)
• Consequence: PFKP NM_002627.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFKP	NM_002627.5	c.186+4992C>T		intron_variant	Intron 2 of 21	ENST00000381125.9	NP_002618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKP	ENST00000381125.9	c.186+4992C>T		intron_variant	Intron 2 of 21	1	NM_002627.5	ENSP00000370517.4

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69728 AN: 151954 Hom.: 16563 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.459 AC: 69761 AN: 152070 Hom.: 16580 Cov.: 32 AF XY: 0.451 AC XY: 33542 AN XY: 74318

African (AFR) AF: 0.425 AC: 17620 AN: 41482

American (AMR) AF: 0.403 AC: 6168 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2216 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1174 AN: 5168

South Asian (SAS) AF: 0.284 AC: 1368 AN: 4822

European-Finnish (FIN) AF: 0.457 AC: 4827 AN: 10570

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34640 AN: 67964

Other (OTH) AF: 0.503 AC: 1058 AN: 2104

Alfa AF: 0.469 Hom.: 2979

Bravo AF: 0.456

Asia WGS AF: 0.303 AC: 1055 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	0.93
DANN	Benign	0.82
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9630129; hg19: chr10-3129645;