chr9-94617839-C-T
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Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_000507.4(FBP1):c.355G>A(p.Asp119Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,200 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 Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
FBP1
NM_000507.4 missense
NM_000507.4 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 6.07
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 Pathogenic. Variant got 16 ACMG points.
PM1
In a mutagenesis_site Reduced activity. (size 0) in uniprot entity F16P1_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.981
PP5
Variant 9-94617839-C-T is Pathogenic according to our data. Variant chr9-94617839-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 214364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBP1 | NM_000507.4 | c.355G>A | p.Asp119Asn | missense_variant | 3/7 | ENST00000375326.9 | NP_000498.2 | |
FBP1 | NM_001127628.2 | c.355G>A | p.Asp119Asn | missense_variant | 4/8 | NP_001121100.1 | ||
FBP1 | XM_006717005.5 | c.109G>A | p.Asp37Asn | missense_variant | 3/7 | XP_006717068.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBP1 | ENST00000375326.9 | c.355G>A | p.Asp119Asn | missense_variant | 3/7 | 1 | NM_000507.4 | ENSP00000364475.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251346Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135844
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461200Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726948
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fructose-biphosphatase deficiency Pathogenic:2
Pathogenic, criteria provided, single submitter | in vitro | Department of Medical Genetics, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine | Mar 27, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Molecular Medicine, Children’s Hospital of Fudan University | Dec 21, 2022 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 15, 2014 | p.Asp119Asn (GAT>AAT): c.355 G>A in exon 3 of the FBP1 gene (NM_000507.3). It has not been reported as a benign polymorphism to our knowledge. It has been presented as a mutation in association with fructose 1,6-bisphosphatase deficiency in a poster session (Frisso et al., 2013). The D119N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
.;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Loss of stability (P = 0.1353);Loss of stability (P = 0.1353);.;
MVP
MPC
0.98
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at