Genetic Variant FBP1:p.Leu326Phe (chr9-94603422-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000507.4(FBP1):c.976C>T(p.Leu326Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L326V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

FBP1
NM_000507.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.351

Publications

2 publications found

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]

FBP1 links:

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

PCAT7 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11299184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBP1	NM_000507.4 link	c.976C>T	p.Leu326Phe	missense_variant	Exon 7 of 7	ENST00000375326.9	NP_000498.2	P09467
FBP1	NM_001127628.2 link	c.976C>T	p.Leu326Phe	missense_variant	Exon 8 of 8		NP_001121100.1	P09467Q2TU34
FBP1	XM_006717005.5 link	c.730C>T	p.Leu244Phe	missense_variant	Exon 7 of 7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9 link	c.976C>T	p.Leu326Phe	missense_variant	Exon 7 of 7	1	NM_000507.4	ENSP00000364475.5		P09467

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251120

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.000134

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111968

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.19

.;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.34

LIST_S2

Uncertain

0.88

D;.;T

M_CAP

Benign

0.076

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.99

.;L;L

PhyloP100

0.35

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.47

.;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0050

.;D;D

Sift4G

Uncertain

0.015

.;D;D

Polyphen

0.0090

.;B;B

Vest4

0.079

MutPred

0.46

.;Gain of methylation at K330 (P = 0.0744);Gain of methylation at K330 (P = 0.0744);

MVP

0.49

MPC

0.32

ClinPred

0.15

GERP RS

-5.4

Varity_R

0.18

gMVP

0.31

Mutation Taster

=90/10

polymorphism

(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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chr9-94603422-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over