rs121918188

Variant names:

• chr9-94609998-C-G
• rs121918188
• NM_000507.4:c.490G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-94609998-C-G
• chr9-94609998-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2 PM5 PP3_Strong

The NM_000507.4(FBP1):​c.490G>C​(p.Gly164Arg) variant causes a missense 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. 13/22 in silico tools predict a damaging 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. G164S) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBP1 NM_000507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 22 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]

FBP1 Gene-Disease associations (from GenCC):

• fructose-1,6-bisphosphatase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr9-94609998-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.993

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBP1	NM_000507.4	c.490G>C	p.Gly164Arg	missense_variant	Exon 4 of 7	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.490G>C	p.Gly164Arg	missense_variant	Exon 5 of 8		NP_001121100.1
FBP1	XM_006717005.5	c.244G>C	p.Gly82Arg	missense_variant	Exon 4 of 7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.490G>C	p.Gly164Arg	missense_variant	Exon 4 of 7	1	NM_000507.4	ENSP00000364475.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0	.;D;D;D
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D;.;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.99	D;D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Benign	0.0	.;H;H;.
PhyloP100		7.9
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.0	.;D;D;D
REVEL	Benign	0.0
Sift	Pathogenic	0.0	.;D;D;D
Sift4G	Pathogenic	0.0	.;D;D;D
Vest4		0.0
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.99
gMVP		0.99
Mutation Taster		=14/86	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs121918188; hg19: chr9-97372280;