NM_012179.4(FBXO7):c.1388C>T (p.Ser463Leu) AND Parkinsonian-pyramidal syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 24, 2021
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:: RCV001960140.5

Allele description [Variation Report for NM_012179.4(FBXO7):c.1388C>T (p.Ser463Leu)]

NM_012179.4(FBXO7):c.1388C>T (p.Ser463Leu)

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.1388C>T (p.Ser463Leu)

HGVS:

NC_000022.11:g.32498349C>T
NG_016001.2:g.28630C>T
NM_001033024.2:c.1151C>T
NM_001257990.2:c.1046C>T
NM_012179.4:c.1388C>TMANE SELECT
NP_001028196.1:p.Ser384Leu
NP_001244919.1:p.Ser349Leu
NP_036311.3:p.Ser463Leu
NC_000022.10:g.32894336C>T
NM_012179.3:c.1388C>T

Protein change:

S349L

Links:

dbSNP: rs1182785309

NCBI 1000 Genomes Browser:

rs1182785309

Molecular consequence:

NM_001033024.2:c.1151C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257990.2:c.1046C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_012179.4:c.1388C>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002211256	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 24, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002789454	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 18, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002211256

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 24, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002789454

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 18, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Invitae, SCV002211256.2

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

Description

This sequence change replaces serine with leucine at codon 463 of the FBXO7 protein (p.Ser463Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FBXO7-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Fulgent Genetics, Fulgent Genetics, SCV002789454.1

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

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

Last Updated: May 1, 2024

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