NM_000286.3(PEX12):c.102A>T (p.Arg34Ser) AND not specified

Germline classification:: Benign/Likely benign (5 submissions)
Last evaluated:: Jun 14, 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:: RCV000078560.22

Allele description [Variation Report for NM_000286.3(PEX12):c.102A>T (p.Arg34Ser)]

NM_000286.3(PEX12):c.102A>T (p.Arg34Ser)

Gene:

PEX12:peroxisomal biogenesis factor 12 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_000286.3(PEX12):c.102A>T (p.Arg34Ser)

HGVS:

NC_000017.11:g.35577920T>A
NG_008447.1:g.5718A>T
NM_000286.3:c.102A>TMANE SELECT
NP_000277.1:p.Arg34Ser
NP_000277.1:p.Arg34Ser
NC_000017.10:g.33904939T>A
NM_000286.2:c.102A>T
O00623:p.Arg34Ser

Protein change:

R34S

Links:

UniProtKB: O00623#VAR_058389; dbSNP: rs147530802

NCBI 1000 Genomes Browser:

rs147530802

Molecular consequence:

NM_000286.3:c.102A>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Tricholoma sp. 30 XXD-2021 isolate WGS573 voucher KUN-HKAS 107577 Cct4 protein (...
Tricholoma sp. 30 XXD-2021 isolate WGS573 voucher KUN-HKAS 107577 Cct4 protein (Cct4) gene, partial cds
gi|2288962516|gb|MW743944.1|

Nucleotide
Tricholoma sp. 24 XXD-2021 isolate WGS506 voucher KUN-HKAS 107576 Cct4 protein (...
Tricholoma sp. 24 XXD-2021 isolate WGS506 voucher KUN-HKAS 107576 Cct4 protein (Cct4) gene, partial cds
gi|2288962514|gb|MW743943.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000110416	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Benign (May 2, 2014)	germline	clinical testing	Citation Link,
SCV000540016	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Mar 28, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001927793	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV001973842	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV002555864	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Jun 14, 2022)	germline	clinical testing	Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	4	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Eurofins Ntd Llc (ga), SCV000110416.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	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		4	not provided	not provided	not provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000540016.1

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

Description

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Benign by Emory 2014. Has been reported in 2 homozygous individuals of iranian origin, who presented with peroxisomal biogenesis disorder with mild clinical phenotype. Consanguinity in at least one of the families. (Zeharia 2007). Given the high frequency in ExAC, LB

#	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 Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001927793.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001973842.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002555864.1

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

Description

Variant summary: PEX12 c.102A>T (p.Arg34Ser) results in a non-conservative amino acid change located in the Pex, N-terminal domain (IPR006845) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0058 in 282832 control chromosomes in the gnomAD database, including 17 homozygotes. The observed variant frequency is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in PEX12 causing Zellweger Syndrome (0.0016), strongly suggesting that the variant is benign. Six ClinVar submitters have assessed the variant since 2014: two classified the variant as likely benign and four as benign. Based on the evidence outlined above, the variant was classified as benign.

#	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: Nov 3, 2024

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