rs984216789

Variant names:

• chr10-3067617-G-A
• rs984216789
• NM_002627.5:c.22G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-3067617-G-A
• chr10-3067617-G-C
• chr10-3067617-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002627.5(PFKP):​c.22G>A​(p.Ala8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A8P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PFKP NM_002627.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060302317).

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.22G>A	p.Ala8Thr	missense	Exon 1 of 22	NP_002618.1	Q01813-1
	PFKP	NM_001410880.1		c.22G>A	p.Ala8Thr	missense	Exon 1 of 23	NP_001397809.1	A0A8V8TMY4
	PFKP	NM_001323068.2		c.22G>A	p.Ala8Thr	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.22G>A	p.Ala8Thr	missense	Exon 1 of 22	ENSP00000370517.4	Q01813-1
	PFKP	ENST00000699222.1		c.22G>A	p.Ala8Thr	missense	Exon 1 of 23	ENSP00000514216.1	A0A8V8TMY4
	PFKP	ENST00000963518.1		c.22G>A	p.Ala8Thr	missense	Exon 1 of 22	ENSP00000633577.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1377412 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 679628

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29138

American (AMR) AF: 0.00 AC: 0 AN: 34718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24486

East Asian (EAS) AF: 0.00 AC: 0 AN: 32716

South Asian (SAS) AF: 0.00 AC: 0 AN: 77950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069560

Other (OTH) AF: 0.00 AC: 0 AN: 57188

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.4
DANN	Benign	0.95
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.38	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.058
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.092
Sift	Benign	0.43	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.19		Gain of phosphorylation at A8 (P = 0.0078)
MVP		0.099
MPC		0.19
ClinPred		0.055	T
GERP RS		-3.6
PromoterAI		-0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.017
gMVP		0.17
Mutation Taster		=100/0	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: rs984216789; hg19: chr10-3109809;