NM_012179.4(FBXO7):c.1A>C (p.Met1Leu) AND Parkinsonian-pyramidal syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003611390.2

Allele description [Variation Report for NM_012179.4(FBXO7):c.1A>C (p.Met1Leu)]

NM_012179.4(FBXO7):c.1A>C (p.Met1Leu)

Gene:

FBXO7:F-box protein 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.3

Genomic location:

Preferred name:

NM_012179.4(FBXO7):c.1A>C (p.Met1Leu)

HGVS:

NC_000022.11:g.32475003A>C
NG_016001.2:g.5284A>C
NG_145486.1:g.533A>C
NG_145486.2:g.533A>C
NG_145487.1:g.32A>C
NM_012179.4:c.1A>CMANE SELECT
NP_036311.3:p.Met1Leu
NC_000022.10:g.32870990A>C

Protein change:

M1L

Molecular consequence:

NM_012179.4:c.1A>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_012179.4:c.1A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Parkinsonian-pyramidal syndrome
Synonyms:: PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE; Pallidopyramidal syndrome; Pallido-pyramidal disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009830; MedGen: C1850100; Orphanet: 171695; OMIM: 260300

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LOC105778347 [Gossypium raimondii]
LOC105778347 [Gossypium raimondii]
Gene ID:105778347

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004512077	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 15, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19038853, 21347293, 23933751, 26310625, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004512077

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 15, 2023)

germline

clinical testing

PubMed (5)
[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

FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome.

Di Fonzo A, Dekker MC, Montagna P, Baruzzi A, Yonova EH, Correia Guedes L, Szczerbinska A, Zhao T, Dubbel-Hulsman LO, Wouters CH, de Graaff E, Oyen WJ, Simons EJ, Breedveld GJ, Oostra BA, Horstink MW, Bonifati V.

Neurology. 2009 Jan 20;72(3):240-5. doi: 10.1212/01.wnl.0000338144.10967.2b. Epub 2008 Nov 26.

PubMed [citation]

PMID:: 19038853

Loss of nuclear activity of the FBXO7 protein in patients with parkinsonian-pyramidal syndrome (PARK15).

Zhao T, De Graaff E, Breedveld GJ, Loda A, Severijnen LA, Wouters CH, Verheijen FW, Dekker MC, Montagna P, Willemsen R, Oostra BA, Bonifati V.

PLoS One. 2011 Feb 11;6(2):e16983. doi: 10.1371/journal.pone.0016983.

PubMed [citation]

PMID:: 21347293
PMCID:: PMC3037939

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004512077.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects the initiator methionine of the FBXO7 mRNA. The next in-frame methionine is located at codon 115. This variant is present in population databases (rs753392528, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with FBXO7-related conditions. This variant disrupts a region of the FBXO7 protein in which other variant(s) (p.Thr22Met) have been determined to be pathogenic (PMID: 19038853, 21347293, 23933751, 26310625). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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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