chr10-3101408-C-A

Variant names:

• chr10-3101408-C-A
• rs376660415
• NM_002627.5:c.308C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002627.5(PFKP):​c.308C>A​(p.Thr103Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. T103M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PFKP NM_002627.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25763264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFKP	NM_002627.5	c.308C>A	p.Thr103Lys	missense_variant	Exon 4 of 22	ENST00000381125.9	NP_002618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKP	ENST00000381125.9	c.308C>A	p.Thr103Lys	missense_variant	Exon 4 of 22	1	NM_002627.5	ENSP00000370517.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000438 AC: 1 AN: 228396 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124256

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000982

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451128 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 721132

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.34	.;T;.;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.9	.;L;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	.;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.036	.;D;T;D
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.30	.;B;.;.
Vest4		0.44, 0.46
MutPred		0.61		.;Gain of MoRF binding (P = 0.0385);.;.;
MVP		0.45
MPC		0.38
ClinPred		0.16	T
GERP RS		-0.085
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.84

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: rs376660415; hg19: chr10-3143600;