Genetic Variant FBP2:p.Met249Thr (chr9-94563421-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_003837.4(FBP2):c.746T>C(p.Met249Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,788 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: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

FBP2
NM_003837.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.02

Publications

0 publications found

Variant links:

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]

FBP2 links:

PCAT7 (HGNC:48824): (prostate cancer associated transcript 7)

PCAT7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.96

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBP2	NM_003837.4 link	c.746T>C	p.Met249Thr	missense_variant	Exon 6 of 7	ENST00000375337.4	NP_003828.2	O00757

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP2	ENST00000375337.4 link	c.746T>C	p.Met249Thr	missense_variant	Exon 6 of 7	1	NM_003837.4	ENSP00000364486.3		O00757

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1111942

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 06, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.746T>C (p.M249T) alteration is located in exon 6 (coding exon 6) of the FBP2 gene. This alteration results from a T to C substitution at nucleotide position 746, causing the methionine (M) at amino acid position 249 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.67

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.96

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

4.4

PhyloP100

9.0

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.95

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.96

Vest4

0.91

MutPred

0.83

Gain of glycosylation at S248 (P = 0.0163);

MVP

0.94

MPC

0.36

ClinPred

1.0

GERP RS

4.8

Varity_R

0.94

gMVP

0.86

Mutation Taster

=6/94

disease causing

(source)

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

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9-94563421-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over