rs121918191

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The ENST00000375326.9(FBP1):ā€‹c.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

Scores

15
3
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.32
Variant links:
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]

Genome browser will be placed here

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
FBP1NM_000507.4 linkuse as main transcriptc.581T>C p.Phe194Ser missense_variant 5/7 ENST00000375326.9 NP_000498.2
FBP1NM_001127628.2 linkuse as main transcriptc.581T>C p.Phe194Ser missense_variant 6/8 NP_001121100.1
FBP1XM_006717005.5 linkuse as main transcriptc.335T>C p.Phe112Ser missense_variant 5/7 XP_006717068.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBP1ENST00000375326.9 linkuse as main transcriptc.581T>C p.Phe194Ser missense_variant 5/71 NM_000507.4 ENSP00000364475 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461820
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
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 providedliterature onlyOMIMJul 01, 2002- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.45
D
BayesDel_noAF
Pathogenic
0.41
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.91
.;D;D;D
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.95
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
1.0
D;.;D;D
M_CAP
Pathogenic
0.35
D
MetaRNN
Pathogenic
0.98
D;D;D;D
MetaSVM
Pathogenic
0.95
D
MutationAssessor
Pathogenic
4.4
.;H;H;.
MutationTaster
Benign
1.0
A;A
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-7.9
.;D;D;D
REVEL
Pathogenic
0.96
Sift
Pathogenic
0.0
.;D;D;D
Sift4G
Pathogenic
0.0
.;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
1.0
D
GERP RS
5.4
Varity_R
0.99
gMVP
0.98

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121918191; hg19: chr9-97369221; API