rs1064891

Variant names:

• chr10-6234611-T-C
• rs1064891
• NM_004566.4:c.*1669T>C

Variant summary

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

The NM_001282630.3(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_001282630.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282630.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKFB3	NM_004566.4	MANE Select	c.*1669T>C		3_prime_UTR	Exon 15 of 15	NP_004557.1
	PFKFB3	NM_001282630.3		c.*1669T>C		3_prime_UTR	Exon 15 of 15	NP_001269559.1
	PFKFB3	NM_001314063.2		c.*1710T>C		3_prime_UTR	Exon 16 of 16	NP_001300992.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKFB3	ENST00000379775.9	TSL:1 MANE Select	c.*1669T>C		3_prime_UTR	Exon 15 of 15	ENSP00000369100.4
	PFKFB3	ENST00000379789.8	TSL:1	c.*1669T>C		3_prime_UTR	Exon 15 of 15	ENSP00000369115.4
	PFKFB3	ENST00000937282.1		c.*1669T>C		3_prime_UTR	Exon 15 of 15	ENSP00000607341.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.336 AC: 39 AN: 116

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.46
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1064891; hg19: chr10-6276574;