chr10-3067612-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_002627.5(PFKP):​c.17C>A​(p.Ser6Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000785 in 1,529,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S6F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: PFKP NM_002627.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986

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 Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity PFKAP_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20548692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFKP	NM_002627.5	c.17C>A	p.Ser6Tyr	missense_variant	Exon 1 of 22	ENST00000381125.9	NP_002618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKP	ENST00000381125.9	c.17C>A	p.Ser6Tyr	missense_variant	Exon 1 of 22	1	NM_002627.5	ENSP00000370517.4
PFKP	ENST00000699222.1	c.17C>A	p.Ser6Tyr	missense_variant	Exon 1 of 23			ENSP00000514216.1
PFKP	ENST00000607886.5	c.-3+1190C>A		intron_variant	Intron 1 of 3	5		ENSP00000477128.1
PFKP	ENST00000495715.1	n.-60C>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000799 AC: 11 AN: 1377276 Hom.: 0 Cov.: 30 AF XY: 0.0000103 AC XY: 7 AN XY: 679582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000935

Gnomad4 OTH exome AF: 0.0000175

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.19
Sift	Benign	0.033	D
Sift4G	Uncertain	0.012	D
Polyphen		0.45	P
Vest4		0.20
MutPred		0.29		Loss of disorder (P = 0.025);
MVP		0.40
MPC		0.25
ClinPred		0.13	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.064
gMVP		0.47

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: rs1401039990; hg19: chr10-3109804;