rs121918191
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The ENST00000375326.9(FBP1):āc.581T>Cā(p.Phe194Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
FBP1
ENST00000375326.9 missense
ENST00000375326.9 missense
Scores
15
3
1
Clinical Significance
Conservation
PhyloP100: 9.32
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.983
PP5
Variant 9-94606939-A-G is Pathogenic according to our data. Variant chr9-94606939-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 871.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBP1 | NM_000507.4 | c.581T>C | p.Phe194Ser | missense_variant | 5/7 | ENST00000375326.9 | NP_000498.2 | |
FBP1 | NM_001127628.2 | c.581T>C | p.Phe194Ser | missense_variant | 6/8 | NP_001121100.1 | ||
FBP1 | XM_006717005.5 | c.335T>C | p.Phe112Ser | missense_variant | 5/7 | XP_006717068.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBP1 | ENST00000375326.9 | c.581T>C | p.Phe194Ser | missense_variant | 5/7 | 1 | NM_000507.4 | ENSP00000364475 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461820Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 727214
GnomAD4 exome
AF:
AC:
1
AN:
1461820
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
727214
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Fructose-biphosphatase deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2002 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;H;H;.
MutationTaster
Benign
A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
.;D;D;D
Sift4G
Pathogenic
.;D;D;D
Polyphen
1.0
.;D;D;.
Vest4
0.94, 0.94
MutPred
0.91
.;Loss of stability (P = 0.0386);Loss of stability (P = 0.0386);.;
MVP
0.98
MPC
1.4
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at