NM_004562.3(PRKN):c.247A>G (p.Thr83Ala) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 17, 2022
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:: RCV002032396.13

Allele description [Variation Report for NM_004562.3(PRKN):c.247A>G (p.Thr83Ala)]

NM_004562.3(PRKN):c.247A>G (p.Thr83Ala)

Gene:

PRKN:parkin RBR E3 ubiquitin protein ligase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q26

Genomic location:

Preferred name:

NM_004562.3(PRKN):c.247A>G (p.Thr83Ala)

HGVS:

NC_000006.12:g.162262690T>C
NG_008289.2:g.470113A>G
NM_004562.3:c.247A>GMANE SELECT
NM_013987.3:c.247A>G
NM_013988.3:c.171+180620A>G
NP_004553.2:p.Thr83Ala
NP_054642.2:p.Thr83Ala
NC_000006.11:g.162683722T>C
NC_000006.11:g.162683722T>C
NM_004562.2:c.247A>G

Protein change:

T83A

Links:

dbSNP: rs141825163

NCBI 1000 Genomes Browser:

rs141825163

Molecular consequence:

NM_013988.3:c.171+180620A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_004562.3:c.247A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_013987.3:c.247A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002009823	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 3, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002139361	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 17, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28862745, 25939424, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002009823

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 3, 2021)

germline

clinical testing

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

SCV002139361

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 17, 2022)

germline

clinical testing

PubMed (3)
[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	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Diagnostic exome sequencing in early-onset Parkinson's disease confirms VPS13C as a rare cause of autosomal-recessive Parkinson's disease.

Schormair B, Kemlink D, Mollenhauer B, Fiala O, Machetanz G, Roth J, Berutti R, Strom TM, Haslinger B, Trenkwalder C, Zahorakova D, Martasek P, Ruzicka E, Winkelmann J.

Clin Genet. 2018 Mar;93(3):603-612. doi: 10.1111/cge.13124. Epub 2018 Jan 24.

PubMed [citation]

PMID:: 28862745

See all PubMed Citations (4)

Details of each submission

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002009823.3

#	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	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002139361.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 83 of the PRKN protein (p.Thr83Ala). This variant is present in population databases (rs141825163, gnomAD 0.07%). This missense change has been observed in individual(s) with early-onset Parkinson's disease (PMID: 28862745). ClinVar contains an entry for this variant (Variation ID: 903886). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects PRKN function (PMID: 25939424). 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

Last Updated: Jun 9, 2024

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