NM_024876.4(COQ8B):c.532C>T (p.Arg178Trp) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 3, 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:: RCV004019521.1

Allele description [Variation Report for NM_024876.4(COQ8B):c.532C>T (p.Arg178Trp)]

NM_024876.4(COQ8B):c.532C>T (p.Arg178Trp)

Gene:

COQ8B:coenzyme Q8B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_024876.4(COQ8B):c.532C>T (p.Arg178Trp)

HGVS:

NC_000019.10:g.40705140G>A
NG_027800.1:g.16746C>T
NM_001142555.3:c.409C>T
NM_024876.4:c.532C>TMANE SELECT
NP_001136027.1:p.Arg137Trp
NP_079152.3:p.Arg178Trp
NP_079152.3:p.Arg178Trp
NC_000019.9:g.41211045G>A
NM_001142555.2:c.409C>T
NM_024876.3:c.532C>T
Q96D53:p.Arg178Trp

Protein change:

R137W; ARG178TRP

Links:

UniProtKB: Q96D53#VAR_070552; OMIM: 615567.0001; dbSNP: rs398122978

NCBI 1000 Genomes Browser:

rs398122978

Molecular consequence:

NM_001142555.3:c.409C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024876.4:c.532C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004850475	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Nov 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24270420, 32859164, 36177613, 36532926 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004850475

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Nov 3, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption.

Ashraf S, Gee HY, Woerner S, Xie LX, Vega-Warner V, Lovric S, Fang H, Song X, Cattran DC, Avila-Casado C, Paterson AD, Nitschké P, Bole-Feysot C, Cochat P, Esteve-Rudd J, Haberberger B, Allen SJ, Zhou W, Airik R, Otto EA, Barua M, Al-Hamed MH, et al.

J Clin Invest. 2013 Dec;123(12):5179-89. doi: 10.1172/JCI69000. Epub 2013 Nov 25.

PubMed [citation]

PMID:: 24270420
PMCID:: PMC3859425

A case report of adult-onset COQ8B nephropathy presenting focal segmental glomerulosclerosis with granular swollen podocytes.

Maeoka Y, Doi T, Aizawa M, Miyasako K, Hirashio S, Masuda Y, Kishita Y, Okazaki Y, Murayama K, Imasawa T, Hara S, Masaki T.

BMC Nephrol. 2020 Aug 28;21(1):376. doi: 10.1186/s12882-020-02040-z.

PubMed [citation]

PMID:: 32859164
PMCID:: PMC7456044

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV004850475.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The c.532C>T (p.R178W) alteration is located in exon 7 (coding exon 6) of the COQ8B gene. This alteration results from a C to T substitution at nucleotide position 532, causing the arginine (R) at amino acid position 178 to be replaced by a tryptophan (W). Based on data from gnomAD, the T allele has an overall frequency of 0.003% (7/279154) total alleles studied. The highest observed frequency was 0.02% (4/19808) of East Asian alleles. This alteration was detected in the homozygous state in multiple individuals with COQ8B-related primary coenzyme Q10 deficiency (Al-Hamed, 2022; Alvi, 2022; Maeoka, 2020; Ashraf, 2013). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely 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: May 3, 2025

ClinVar

Relating variation to medicine