chr10-3113161-C-T

Variant names:

• chr10-3113161-C-T
• rs3816699
• NM_002627.5:c.1197C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002627.5(PFKP):​c.1197C>T​(p.Ile399Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,612,188 control chromosomes in the GnomAD database, including 18,807 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 0.15 (1954 hom., cov: 35)
  • Exomes 𝑓: 0.15 (16853 hom.)
• Consequence: PFKP NM_002627.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 18 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.357 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 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.1197C>T	p.Ile399Ile	synonymous	Exon 12 of 22	NP_002618.1
	PFKP	NM_001410880.1		c.1197C>T	p.Ile399Ile	synonymous	Exon 12 of 23	NP_001397809.1
	PFKP	NM_001242339.2		c.1173C>T	p.Ile391Ile	synonymous	Exon 14 of 24	NP_001229268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKP	ENST00000381125.9	TSL:1 MANE Select	c.1197C>T	p.Ile399Ile	synonymous	Exon 12 of 22	ENSP00000370517.4
	PFKP	ENST00000699222.1		c.1197C>T	p.Ile399Ile	synonymous	Exon 12 of 23	ENSP00000514216.1
	PFKP	ENST00000381075.7	TSL:2	c.1083C>T	p.Ile361Ile	synonymous	Exon 13 of 23	ENSP00000370465.3

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23382 AN: 152182 Hom.: 1951 Cov.: 35

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.149 AC: 37098 AN: 248152 AF XY: 0.145

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.0655

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.149 AC: 217406 AN: 1459888 Hom.: 16853 Cov.: 38 AF XY: 0.146 AC XY: 106324 AN XY: 726082

African (AFR) AF: 0.160 AC: 5366 AN: 33450

American (AMR) AF: 0.205 AC: 9134 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 5842 AN: 26116

East Asian (EAS) AF: 0.0745 AC: 2954 AN: 39654

South Asian (SAS) AF: 0.0719 AC: 6181 AN: 85986

European-Finnish (FIN) AF: 0.159 AC: 8410 AN: 53000

Middle Eastern (MID) AF: 0.158 AC: 910 AN: 5766

European-Non Finnish (NFE) AF: 0.153 AC: 169575 AN: 1111134

Other (OTH) AF: 0.150 AC: 9034 AN: 60314

GnomAD4 genome AF: 0.154 AC: 23398 AN: 152300 Hom.: 1954 Cov.: 35 AF XY: 0.150 AC XY: 11193 AN XY: 74482

African (AFR) AF: 0.150 AC: 6249 AN: 41576

American (AMR) AF: 0.179 AC: 2744 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3470

East Asian (EAS) AF: 0.0608 AC: 315 AN: 5178

South Asian (SAS) AF: 0.0674 AC: 326 AN: 4834

European-Finnish (FIN) AF: 0.149 AC: 1581 AN: 10616

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10819 AN: 68006

Other (OTH) AF: 0.155 AC: 327 AN: 2114

Alfa AF: 0.161 Hom.: 4232

Bravo AF: 0.161

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.4
DANN	Benign	0.76
PhyloP100		-0.36
PromoterAI		-0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3816699; hg19: chr10-3155353; COSMIC: COSV101126974; COSMIC: COSV101126974;