chr10-3101437-A-C

Position:

• chr10-3101437-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002627.5(PFKP):​c.337A>C​(p.Asn113His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PFKP NM_002627.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.03

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKP	NM_002627.5	c.337A>C	p.Asn113His	missense_variant	4/22	ENST00000381125.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKP	ENST00000381125.9	c.337A>C	p.Asn113His	missense_variant	4/22	1	NM_002627.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.337A>C (p.N113H) alteration is located in exon 4 (coding exon 4) of the PFKP gene. This alteration results from a A to C substitution at nucleotide position 337, causing the asparagine (N) at amino acid position 113 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	0.12
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.78	D;D;D;D
MetaSVM	Uncertain	0.14	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
Sift4G	Uncertain	0.046	D;T;T;T
Polyphen		0.64	.;P;.;.
Vest4		0.60, 0.62
MutPred		0.52		.;Gain of catalytic residue at L115 (P = 0.0943);.;.;
MVP		0.72
MPC		0.42
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.90
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1329884849; hg19: chr10-3143629;