9-94559128-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_003837.4(FBP2):c.830G>T(p.Arg277Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,609,562 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
FBP2
NM_003837.4 missense
NM_003837.4 missense
Scores
15
3
1
Clinical Significance
Conservation
PhyloP100: 7.40
Genes affected
FBP2 (HGNC:3607): (fructose-bisphosphatase 2) This gene encodes a gluconeogenesis regulatory enzyme which catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.946
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBP2 | NM_003837.4 | c.830G>T | p.Arg277Leu | missense_variant | 7/7 | ENST00000375337.4 | |
PCAT7 | NR_121566.2 | n.546C>A | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBP2 | ENST00000375337.4 | c.830G>T | p.Arg277Leu | missense_variant | 7/7 | 1 | NM_003837.4 | P1 | |
PCAT7 | ENST00000647389.1 | n.417C>A | non_coding_transcript_exon_variant | 2/9 | |||||
PCAT7 | ENST00000452148.3 | n.417C>A | non_coding_transcript_exon_variant | 2/3 | 2 | ||||
PCAT7 | ENST00000644721.1 | n.423C>A | non_coding_transcript_exon_variant | 2/3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152112Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250450Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135334
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GnomAD4 exome AF: 0.00000618 AC: 9AN: 1457450Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3AN XY: 724248
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74308
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 18, 2024 | The c.830G>T (p.R277L) alteration is located in exon 7 (coding exon 7) of the FBP2 gene. This alteration results from a G to T substitution at nucleotide position 830, causing the arginine (R) at amino acid position 277 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at K273 (P = 0.0495);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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