10-3113348-A-G

Variant names:

• chr10-3113348-A-G
• rs4881085
• NM_002627.5:c.1225-24A>G

Variant summary

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

The NM_002627.5(PFKP):​c.1225-24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 1,573,858 control chromosomes in the GnomAD database, including 625,647 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 0.84 (54948 hom., cov: 36)
  • Exomes 𝑓: 0.90 (570699 hom.)
• Consequence: PFKP NM_002627.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734
• Publications: 15 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002627.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKP	NM_002627.5	MANE Select	c.1225-24A>G		intron	N/A	NP_002618.1
	PFKP	NM_001410880.1		c.1225-24A>G		intron	N/A	NP_001397809.1
	PFKP	NM_001242339.2		c.1201-24A>G		intron	N/A	NP_001229268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKP	ENST00000381125.9	TSL:1 MANE Select	c.1225-24A>G		intron	N/A	ENSP00000370517.4
	PFKP	ENST00000699222.1		c.1225-24A>G		intron	N/A	ENSP00000514216.1
	PFKP	ENST00000381075.7	TSL:2	c.1111-24A>G		intron	N/A	ENSP00000370465.3

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128486 AN: 152170 Hom.: 54933 Cov.: 36

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.866

GnomAD2 exomes AF: 0.893 AC: 202034 AN: 226332 AF XY: 0.899

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.894

Gnomad ASJ exome AF: 0.919

Gnomad EAS exome AF: 0.986

Gnomad FIN exome AF: 0.890

Gnomad NFE exome AF: 0.895

Gnomad OTH exome AF: 0.889

GnomAD4 exome AF: 0.895 AC: 1272700 AN: 1421570 Hom.: 570699 Cov.: 40 AF XY: 0.898 AC XY: 629200 AN XY: 700924

African (AFR) AF: 0.691 AC: 22679 AN: 32808

American (AMR) AF: 0.893 AC: 37798 AN: 42330

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 21524 AN: 23566

East Asian (EAS) AF: 0.992 AC: 38836 AN: 39142

South Asian (SAS) AF: 0.937 AC: 75124 AN: 80182

European-Finnish (FIN) AF: 0.894 AC: 46217 AN: 51674

Middle Eastern (MID) AF: 0.927 AC: 5188 AN: 5598

European-Non Finnish (NFE) AF: 0.895 AC: 973145 AN: 1087674

Other (OTH) AF: 0.891 AC: 52189 AN: 58596

GnomAD4 genome AF: 0.844 AC: 128543 AN: 152288 Hom.: 54948 Cov.: 36 AF XY: 0.844 AC XY: 62882 AN XY: 74466

African (AFR) AF: 0.695 AC: 28868 AN: 41546

American (AMR) AF: 0.868 AC: 13279 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 3164 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5105 AN: 5174

South Asian (SAS) AF: 0.940 AC: 4539 AN: 4830

European-Finnish (FIN) AF: 0.891 AC: 9464 AN: 10618

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61157 AN: 68024

Other (OTH) AF: 0.867 AC: 1835 AN: 2116

Alfa AF: 0.889 Hom.: 28555

Bravo AF: 0.836

Asia WGS AF: 0.943 AC: 3279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.25
PhyloP100		-0.73
PromoterAI		-0.016	Neutral
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: rs4881085; hg19: chr10-3155540;