NM_024876.4(COQ8B):c.532C>T (p.Arg178Trp) AND not provided

Germline classification:: Likely pathogenic (4 submissions)
Last evaluated:: Mar 18, 2024
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:: RCV001701490.17

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001932756	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	Pathogenic	germline	clinical testing
SCV001951053	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV001986371	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Mar 18, 2024)	germline	clinical testing	Citation Link,
SCV003443913	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 21, 2022)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 24270420, 28204945, 28454995, 29382012, 31130284, 31937884, 32543055, 32604935, 32859164, 29194833, 28492532

Help

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	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

Spectrum of mutations in Chinese children with steroid-resistant nephrotic syndrome.

Wang F, Zhang Y, Mao J, Yu Z, Yi Z, Yu L, Sun J, Wei X, Ding F, Zhang H, Xiao H, Yao Y, Tan W, Lovric S, Ding J, Hildebrandt F.

Pediatr Nephrol. 2017 Jul;32(7):1181-1192. doi: 10.1007/s00467-017-3590-y. Epub 2017 Feb 15.

PubMed [citation]

PMID:: 28204945
PMCID:: PMC5478193

See all PubMed Citations (11)

Details of each submission

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001932756.1

#	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 Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001951053.1

#	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 GeneDx, SCV001986371.3

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31130284, 29194833, 29382012, 28454995, 36177613, 32859164, 31328266, 34605136, 35483523, 36176665, 35755072, 37217505, 33677064, 36532926, AlsanieW2022[Article], WangY2024[Review], 35683636, 36898413, 36843884, 36034551, 28204945, 35046417, 34638552, 33413146, 32543055, 24270420, 32604935, 31937884)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003443913.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

This missense change has been observed in individuals with steroid-resistant nephrotic syndrome (PMID: 24270420, 28204945, 28454995, 29382012, 31130284, 31937884, 32543055, 32604935, 32859164). It has also been observed to segregate with disease in related individuals. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects COQ8B function (PMID: 29194833). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COQ8B protein function. ClinVar contains an entry for this variant (Variation ID: 91845). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 178 of the COQ8B protein (p.Arg178Trp).

#	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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