NM_000287.4(PEX6):c.1931G>A (p.Arg644Gln) AND Peroxisome biogenesis disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV001240731.4

Allele description [Variation Report for NM_000287.4(PEX6):c.1931G>A (p.Arg644Gln)]

NM_000287.4(PEX6):c.1931G>A (p.Arg644Gln)

Gene:

PEX6:peroxisomal biogenesis factor 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.1

Genomic location:

Preferred name:

NM_000287.4(PEX6):c.1931G>A (p.Arg644Gln)

HGVS:

NC_000006.12:g.42966812C>T
NG_008370.1:g.17432G>A
NM_000287.4:c.1931G>AMANE SELECT
NM_001316313.2:c.1667G>A
NP_000278.3:p.Arg644Gln
NP_001303242.1:p.Arg556Gln
NC_000006.11:g.42934550C>T
NM_000287.3:c.1931G>A
NR_133009.2:n.1962G>A

Protein change:

R556Q

Links:

dbSNP: rs746117128

NCBI 1000 Genomes Browser:

rs746117128

Molecular consequence:

NM_000287.4:c.1931G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001316313.2:c.1667G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_133009.2:n.1962G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Peroxisome biogenesis disorder (PBD, ZSS)
Synonyms:: PEROXISOME BIOGENESIS DISORDER (NEONATAL ADRENOLEUKODYSTROPHY/INFANTILE REFSUM DISEASE); INFANTILE PHYTANIC ACID STORAGE DISEASE; PEROXISOME BIOGENESIS DISORDER (NALD/IRD); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019234; MedGen: C1832200; OMIM: PS214100

Recent activity

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Microbe sample from Pseudarthrobacter sp. strain RMG13
Microbe sample from Pseudarthrobacter sp. strain RMG13

biosample
EF-hand calcium-binding domain-containing protein 7 [Rattus norvegicus]
EF-hand calcium-binding domain-containing protein 7 [Rattus norvegicus]
gi|300798062|ref|NP_001178795.1|

Protein
PREDICTED: Rattus norvegicus EF-hand calcium binding domain 7 (Efcab7), transcri...
PREDICTED: Rattus norvegicus EF-hand calcium binding domain 7 (Efcab7), transcript variant X4, mRNA
gi|2678945298|ref|XM_039110290.2|

Nucleotide
Homo sapiens natriuretic peptide receptor 3 (NPR3), transcript variant 1, mRNA
Homo sapiens natriuretic peptide receptor 3 (NPR3), transcript variant 1, mRNA
gi|1519243051|ref|NM_001204375.2|

Nucleotide
unconventional myosin-If [Rattus norvegicus]
unconventional myosin-If [Rattus norvegicus]
gi|157821107|ref|NP_001101546.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001413700	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34055681, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001413700

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2022)

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

The Leukodystrophy Spectrum in Saudi Arabia: Epidemiological, Clinical, Radiological, and Genetic Data.

Alfadhel M, Almuqbil M, Al Mutairi F, Umair M, Almannai M, Alghamdi M, Althiyab H, Albarakati R, Bashiri FA, Alshuaibi W, Ba-Armah D, Saleh MA, Al-Asmari A, Faqeih E, Altuwaijri W, Al-Rumayyan A, Balwi MA, Ababneh F, Alswaid AF, Eyaid WM, Almontashiri NAM, Alhashem A, et al.

Front Pediatr. 2021;9:633385. doi: 10.3389/fped.2021.633385.

PubMed [citation]

PMID:: 34055681
PMCID:: PMC8155587

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001413700.3

#	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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 644 of the PEX6 protein (p.Arg644Gln). This variant is present in population databases (rs746117128, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of Zellweger syndrome spectrum (PMID: 34055681). ClinVar contains an entry for this variant (Variation ID: 911291). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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: Sep 29, 2024

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