rs3816699

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-3113161-C-G
• chr10-3113161-C-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.1197C>G​(p.Ile399Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PFKP NM_002627.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 0 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: 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=0.22562388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFKP	NM_002627.5	c.1197C>G	p.Ile399Met	missense_variant	Exon 12 of 22	ENST00000381125.9	NP_002618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKP	ENST00000381125.9	c.1197C>G	p.Ile399Met	missense_variant	Exon 12 of 22	1	NM_002627.5	ENSP00000370517.4

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460220 Hom.: 0 Cov.: 38 AF XY: 0.00000413 AC XY: 3 AN XY: 726264

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111346

Other (OTH) AF: 0.0000332 AC: 2 AN: 60328

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.17	T;.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.63	T;T;.
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	-0.55	N;.;.
PhyloP100		-0.36
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.58	N;N;N
REVEL	Benign	0.29
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.63	P;.;.
Vest4		0.23
MutPred		0.75		Gain of ubiquitination at K400 (P = 0.0773);.;.;
MVP		0.60
MPC		0.20
ClinPred		0.14	T
GERP RS		-0.66
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.51
Mutation Taster		=90/10	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: rs3816699; hg19: chr10-3155353;