rs2185691

Positions:

• chr10-6250644-T-C

Variant summary

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

The NM_001363545.2(PFKFB3):​c.1516-3534T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,694 control chromosomes in the GnomAD database, including 1,169 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 0.11 (1169 hom., cov: 30)
• Consequence: PFKFB3 NM_001363545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKFB3	NM_001363545.2	c.1516-3534T>C		intron_variant			NP_001350474.1
PFKFB3	XM_047425341.1	c.1455+24279T>C		intron_variant			XP_047281297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFKFB3	ENST00000640683.1	c.1516-3534T>C		intron_variant		5		ENSP00000492001

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16390 AN: 151604 Hom.: 1164 Cov.: 30

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.108 AC: 16427 AN: 151694 Hom.: 1169 Cov.: 30 AF XY: 0.112 AC XY: 8310 AN XY: 74096

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.0593

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0757 Hom.: 559

Bravo AF: 0.120

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2185691; hg19: chr10-6292607;