10-6234780-G-A

Variant names:

• chr10-6234780-G-A
• rs1539234
• NM_004566.4:c.*1838G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004566.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKFB3	NM_004566.4	MANE Select	c.*1838G>A		3_prime_UTR	Exon 15 of 15	NP_004557.1
	PFKFB3	NR_136554.2		n.3168G>A		non_coding_transcript_exon	Exon 12 of 12
	PFKFB3	NM_001282630.3		c.*1838G>A		3_prime_UTR	Exon 15 of 15	NP_001269559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKFB3	ENST00000379775.9	TSL:1 MANE Select	c.*1838G>A		3_prime_UTR	Exon 15 of 15	ENSP00000369100.4
	PFKFB3	ENST00000379789.8	TSL:1	c.*1838G>A		3_prime_UTR	Exon 15 of 15	ENSP00000369115.4
	PFKFB3	ENST00000360521.7	TSL:5	c.*1879G>A		3_prime_UTR	Exon 16 of 16	ENSP00000353712.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.618 AC: 84 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.417 AC: 5 AN: 12

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.810 AC: 33578 AN: 41454

American (AMR) AF: 0.492 AC: 7501 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2260 AN: 3472

East Asian (EAS) AF: 0.536 AC: 2768 AN: 5164

South Asian (SAS) AF: 0.524 AC: 2525 AN: 4816

European-Finnish (FIN) AF: 0.511 AC: 5396 AN: 10554

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.580 AC: 39445 AN: 67966

Other (OTH) AF: 0.600 AC: 1267 AN: 2112

Alfa AF: 0.586 Hom.: 38605

Bravo AF: 0.633

Asia WGS AF: 0.500 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.59
PhyloP100		-0.19
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: rs1539234; hg19: chr10-6276743;