chr10-3067612-C-T

Variant names:

• chr10-3067612-C-T
• rs1401039990
• NM_002627.5:c.17C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002627.5(PFKP):​c.17C>T​(p.Ser6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000726 in 1,377,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: PFKP NM_002627.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.986
• 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]

PFKP-DT (HGNC:55177): (PFKP divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17791253).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKP	NM_002627.5	MANE Select	c.17C>T	p.Ser6Phe	missense	Exon 1 of 22	NP_002618.1	Q01813-1
	PFKP	NM_001410880.1		c.17C>T	p.Ser6Phe	missense	Exon 1 of 23	NP_001397809.1	A0A8V8TMY4
	PFKP	NM_001323068.2		c.17C>T	p.Ser6Phe	missense	Exon 1 of 21	NP_001309997.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKP	ENST00000381125.9	TSL:1 MANE Select	c.17C>T	p.Ser6Phe	missense	Exon 1 of 22	ENSP00000370517.4	Q01813-1
	PFKP	ENST00000699222.1		c.17C>T	p.Ser6Phe	missense	Exon 1 of 23	ENSP00000514216.1	A0A8V8TMY4
	PFKP	ENST00000963518.1		c.17C>T	p.Ser6Phe	missense	Exon 1 of 22	ENSP00000633577.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000814 AC: 1 AN: 122854 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000232

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000726 AC: 10 AN: 1377278 Hom.: 0 Cov.: 30 AF XY: 0.0000118 AC XY: 8 AN XY: 679582

African (AFR) AF: 0.00 AC: 0 AN: 29126

American (AMR) AF: 0.00 AC: 0 AN: 34698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24494

East Asian (EAS) AF: 0.00 AC: 0 AN: 32694

South Asian (SAS) AF: 0.00 AC: 0 AN: 77924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.00000841 AC: 9 AN: 1069590

Other (OTH) AF: 0.0000175 AC: 1 AN: 57188

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000435 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.70
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.99
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.18
Sift	Benign	0.038	D
Sift4G	Uncertain	0.011	D
Polyphen		0.12	B
Vest4		0.14
MVP		0.36
MPC		0.21
ClinPred		0.10	T
GERP RS		3.2
PromoterAI		0.31	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.058
gMVP		0.50
Mutation Taster		=99/1	polymorphism

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: rs1401039990; hg19: chr10-3109804;