10-6215599-C-T

Variant names:

• chr10-6215599-C-T
• rs2794981
• NM_004566.4:c.299+282C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004566.4(PFKFB3):​c.299+282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,048 control chromosomes in the GnomAD database, including 7,578 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7578 hom., cov: 32)
• Consequence: PFKFB3 NM_004566.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 5 publications found

Genes affected

PFKFB3 (HGNC:8874): (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3) The protein encoded by this gene belongs to a family of bifunctional proteins that are involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate (F2,6BP), and a fructose-2,6-biphosphatase activity that catalyzes the degradation of F2,6BP. This protein is required for cell cycle progression and prevention of apoptosis. It functions as a regulator of cyclin-dependent kinase 1, linking glucose metabolism to cell proliferation and survival in tumor cells. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFKFB3	NM_004566.4	c.299+282C>T		intron_variant	Intron 3 of 14	ENST00000379775.9	NP_004557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKFB3	ENST00000379775.9	c.299+282C>T		intron_variant	Intron 3 of 14	1	NM_004566.4	ENSP00000369100.4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47001 AN: 151930 Hom.: 7580 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.295

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 47022 AN: 152048 Hom.: 7578 Cov.: 32 AF XY: 0.310 AC XY: 23032 AN XY: 74308

African (AFR) AF: 0.396 AC: 16418 AN: 41448

American (AMR) AF: 0.307 AC: 4694 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3470

East Asian (EAS) AF: 0.309 AC: 1596 AN: 5166

South Asian (SAS) AF: 0.348 AC: 1677 AN: 4816

European-Finnish (FIN) AF: 0.251 AC: 2657 AN: 10592

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17810 AN: 67956

Other (OTH) AF: 0.292 AC: 617 AN: 2110

Alfa AF: 0.255 Hom.: 2619

Bravo AF: 0.315

Asia WGS AF: 0.301 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.66
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs2794981; hg19: chr10-6257562;