9-94606867-C-G

Position:

• chr9-94606867-C-G

Variant summary

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

The ENST00000375326.9(FBP1):​c.653G>C​(p.Arg218Thr) 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 ENST00000375326.9 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=0.16311517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBP1	NM_000507.4	c.653G>C	p.Arg218Thr	missense_variant	5/7	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.653G>C	p.Arg218Thr	missense_variant	6/8		NP_001121100.1
FBP1	XM_006717005.5	c.407G>C	p.Arg136Thr	missense_variant	5/7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.653G>C	p.Arg218Thr	missense_variant	5/7	1	NM_000507.4	ENSP00000364475.5

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	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.16	.;T;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.85	D;.;D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	.;L;L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.73	.;N;N;N
REVEL	Benign	0.096
Sift	Benign	0.41	.;T;T;T
Sift4G	Benign	0.56	.;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.15
MutPred		0.63		.;Gain of phosphorylation at R218 (P = 0.0388);Gain of phosphorylation at R218 (P = 0.0388);.;
MVP		0.73
MPC		0.43
ClinPred		0.12	T
GERP RS		1.6
Varity_R		0.32
gMVP		0.61

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;