rs1064891

Positions:

• chr10-6234611-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004566.4(PFKFB3):​c.*1669T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,876 control chromosomes in the GnomAD database, including 11,094 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 0.37 (11089 hom., cov: 30)
  • Exomes 𝑓: 0.33 (5 hom.)
• Consequence: PFKFB3 NM_004566.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKFB3	NM_004566.4	c.*1669T>C		3_prime_UTR_variant	15/15	ENST00000379775.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKFB3	ENST00000379775.9	c.*1669T>C		3_prime_UTR_variant	15/15	1	NM_004566.4
PFKFB3	ENST00000379789.8	c.*1669T>C		3_prime_UTR_variant	15/15	1
PFKFB3	ENST00000360521.7	c.*1710T>C		3_prime_UTR_variant	16/16	5		P4
PFKFB3	ENST00000640683.1	c.1515+8246T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56639 AN: 151632 Hom.: 11081 Cov.: 30

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.415

GnomAD4 exome AF: 0.333 AC: 42 AN: 126 Hom.: 5 Cov.: 0 AF XY: 0.319 AC XY: 23 AN XY: 72

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.373 AC: 56667 AN: 151750 Hom.: 11089 Cov.: 30 AF XY: 0.374 AC XY: 27716 AN XY: 74156

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.413

Alfa AF: 0.407 Hom.: 16910

Bravo AF: 0.374

Asia WGS AF: 0.392 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1064891; hg19: chr10-6276574;