NM_000507.4(FBP1):c.986T>C (p.Leu329Pro) AND Fructose-biphosphatase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Dec 6, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002249045.3

Allele description [Variation Report for NM_000507.4(FBP1):c.986T>C (p.Leu329Pro)]

NM_000507.4(FBP1):c.986T>C (p.Leu329Pro)

Gene:

FBP1:fructose-bisphosphatase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000507.4(FBP1):c.986T>C (p.Leu329Pro)

HGVS:

NC_000009.12:g.94603412A>G
NG_008174.1:g.41838T>C
NM_000507.4:c.986T>CMANE SELECT
NM_001127628.2:c.986T>C
NP_000498.2:p.Leu329Pro
NP_001121100.1:p.Leu329Pro
NC_000009.11:g.97365694A>G
NC_000009.11:g.97365694A>G

Protein change:

L329P

Links:

dbSNP: rs1248299502

NCBI 1000 Genomes Browser:

rs1248299502

Molecular consequence:

NM_000507.4:c.986T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127628.2:c.986T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Fructose-biphosphatase deficiency (FBP1D)
Synonyms:: Baker-Winegrad disease; Fructose-1,6-Diphosphatase Deficiency; Fructose 1,6 Bisphosphatase Deficiency
Identifiers:: MONDO: MONDO:0009251; MedGen: C0016756; Orphanet: 348; OMIM: 229700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002516333	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Likely pathogenic (May 4, 2022)	germline	clinical testing	Citation Link,
SCV004509271	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30858132, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002516333

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2019)

Likely pathogenic
(May 4, 2022)

germline

clinical testing

Citation Link,

SCV004509271

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 6, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic analysis of patients with fructose-1,6-bisphosphatase deficiency.

Pinheiro FC, Sperb-Ludwig F, Ligabue-Braun R, Schüler-Faccini L, de Souza CFM, Vairo F, Schwartz IVD.

Gene. 2019 May 30;699:102-109. doi: 10.1016/j.gene.2019.03.007. Epub 2019 Mar 9.

PubMed [citation]

PMID:: 30858132

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Mendelics, SCV002516333.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004509271.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 329 of the FBP1 protein (p.Leu329Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with fructose-1,6-bisphosphatase deficiency (PMID: 30858132). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1685318). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBP1 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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