Genetic Variant PFKFB3:c.*1669T>C (chr10-6234611-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.105

Publications

10 publications found

Variant links:

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]

PFKFB3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PFKFB3	NM_004566.4 link	c.*1669T>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000379775.9	NP_004557.1	Q16875-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PFKFB3	ENST00000379775.9 link	c.*1669T>C	3_prime_UTR_variant	Exon 15 of 15	1	NM_004566.4	ENSP00000369100.4	Q16875-1
PFKFB3	ENST00000379789.8 link	c.*1669T>C	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000369115.4	Q16875-3
PFKFB3	ENST00000360521.7 link	c.*1710T>C	3_prime_UTR_variant	Exon 16 of 16	5		ENSP00000353712.2	Q16875-2
PFKFB3	ENST00000640683.1 link	c.1515+8246T>C	intron_variant	Intron 14 of 14	5		ENSP00000492001.1	A0A1W2PR17

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56639

AN:

151632

Hom.:

11081

Cov.:

show subpopulations

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:

AN:

126

Hom.:

Cov.:

AF XY:

0.319

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.336

AC:

AN:

116

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.373

AC:

56667

AN:

151750

Hom.:

11089

Cov.:

AF XY:

0.374

AC XY:

27716

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.254

AC:

10494

AN:

41378

American (AMR)

AF:

0.453

AC:

6890

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1287

AN:

3468

East Asian (EAS)

AF:

0.427

AC:

2201

AN:

5160

South Asian (SAS)

AF:

0.412

AC:

1977

AN:

4800

European-Finnish (FIN)

AF:

0.366

AC:

3854

AN:

10520

Middle Eastern (MID)

AF:

0.476

AC:

139

AN:

292

European-Non Finnish (NFE)

AF:

0.419

AC:

28423

AN:

67894

Other (OTH)

AF:

0.413

AC:

869

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1687

3374

5060

6747

8434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.406

Hom.:

20017

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

(source)

DANN

Benign

0.46

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over