rs1769259

chr9-94606867-C-Achr9-94606867-C-Gchr9-94606867-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000507.4(FBP1):c.653G>T(p.Arg218Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R218K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBP1 NM_000507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18990749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBP1	NM_000507.4	c.653G>T	p.Arg218Met	missense_variant	5/7	ENST00000375326.9
FBP1	NM_001127628.2	c.653G>T	p.Arg218Met	missense_variant	6/8
FBP1	XM_006717005.5	c.407G>T	p.Arg136Met	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBP1	ENST00000375326.9	c.653G>T	p.Arg218Met	missense_variant	5/7	1	NM_000507.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	19
Dann	Benign	0.89
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.74	T;.;T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
Polyphen		0.0010	.;B;B;.
Vest4		0.21, 0.21
MutPred		0.62		.;Loss of catalytic residue at R218 (P = 0.129);Loss of catalytic residue at R218 (P = 0.129);.;
MVP		0.76
MPC		0.34
ClinPred		0.34	T
GERP RS		1.6
Varity_R		0.33
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1769259; hg19: chr9-97369149;