rs566453434

Variant names:

• chr9-94603557-C-A
• rs566453434
• NM_000507.4:c.841G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-94603557-C-A
• chr9-94603557-C-T

Variant summary

Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PVS1_Strong PM2 PP5_Very_Strong

The NM_000507.4(FBP1):​c.841G>T​(p.Glu281*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBP1 NM_000507.4 stop_gained
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:2
• Conservation: PhyloP100: 7.73
• Publications: 11 publications found

Genes affected

FBP1 (HGNC:3606): (fructose-bisphosphatase 1) Fructose-1,6-bisphosphatase 1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. Fructose-1,6-diphosphatase deficiency is associated with hypoglycemia and metabolic acidosis. [provided by RefSeq, Jul 2008]

PCAT7 (HGNC:48824): (prostate cancer associated transcript 7)

ACMG classification

Our verdict: Pathogenic. The variant received 14 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 15 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-94603557-C-A is Pathogenic according to our data. Variant chr9-94603557-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 548480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000507.4. 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
	FBP1	NM_000507.4	MANE Select	c.841G>T	p.Glu281*	stop_gained	Exon 7 of 7	NP_000498.2
	FBP1	NM_001127628.2		c.841G>T	p.Glu281*	stop_gained	Exon 8 of 8	NP_001121100.1	P09467

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP1	ENST00000375326.9	TSL:1 MANE Select	c.841G>T	p.Glu281*	stop_gained	Exon 7 of 7	ENSP00000364475.5	P09467
	FBP1	ENST00000884868.1		c.1009G>T	p.Glu337*	stop_gained	Exon 8 of 8	ENSP00000554927.1
	FBP1	ENST00000945615.1		c.1009G>T	p.Glu337*	stop_gained	Exon 7 of 7	ENSP00000615674.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
2	-	-	Fructose-biphosphatase deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	48
DANN	Uncertain	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.96	D
PhyloP100		7.7
Vest4		0.85
GERP RS		5.4
Mutation Taster		=5/195	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs566453434; hg19: chr9-97365839;