rs1539234

chr10-6234780-G-A

Variant summary

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

The NM_004566.4(PFKFB3):c.*1838G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,138 control chromosomes in the GnomAD database, including 31,095 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 0.63 (31069 hom., cov: 30)
  • Exomes 𝑓: 0.60 (26 hom.)
• Consequence: PFKFB3 NM_004566.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKFB3	NM_004566.4	c.*1838G>A		3_prime_UTR_variant	15/15	ENST00000379775.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKFB3	ENST00000379775.9	c.*1838G>A		3_prime_UTR_variant	15/15	1	NM_004566.4
PFKFB3	ENST00000379789.8	c.*1838G>A		3_prime_UTR_variant	15/15	1
PFKFB3	ENST00000360521.7	c.*1879G>A		3_prime_UTR_variant	16/16	5		P4
PFKFB3	ENST00000640683.1	c.1515+8415G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95145 AN: 151870 Hom.: 31018 Cov.: 30

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.601 AC: 89 AN: 148 Hom.: 26 Cov.: 0 AF XY: 0.628 AC XY: 54 AN XY: 86

Gnomad4 EAS exome AF: 0.618

Gnomad4 NFE exome AF: 0.417

GnomAD4 genome AF: 0.627 AC: 95246 AN: 151990 Hom.: 31069 Cov.: 30 AF XY: 0.618 AC XY: 45918 AN XY: 74304

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.600

Alfa AF: 0.584 Hom.: 23245

Bravo AF: 0.633

Asia WGS AF: 0.500 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.2
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1539234; hg19: chr10-6276743;