rs12779447

Positions:

• chr10-6322791-G-A

Variant summary

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

The XM_047425341.1(PFKFB3):​c.1456-3755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,202 control chromosomes in the GnomAD database, including 1,651 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 0.14 (1651 hom., cov: 32)
• Consequence: PFKFB3 XM_047425341.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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]

LINC02649 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKFB3	XM_047425341.1	c.1456-3755G>A		intron_variant			XP_047281297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINC02649	ENST00000399868.2	n.122-3755G>A		intron_variant		2
LINC02649	ENST00000659311.1	n.100-3755G>A		intron_variant
LINC02649	ENST00000670683.1	n.91-3755G>A		intron_variant
LINC02649	ENST00000689295.1	n.81-3755G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21606 AN: 152084 Hom.: 1652 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0167

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.142 AC: 21607 AN: 152202 Hom.: 1651 Cov.: 32 AF XY: 0.138 AC XY: 10287 AN XY: 74412

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.0812

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.120

Alfa AF: 0.167 Hom.: 3026

Bravo AF: 0.137

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.89
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12779447; hg19: chr10-6364754;