NM_024876.4(COQ8B):c.532C>T (p.Arg178Trp) AND Nephrotic syndrome, type 9

Germline classification:: Pathogenic (8 submissions)
Last evaluated:: Mar 17, 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:: RCV000077753.23

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:: Nephrotic syndrome, type 9 (NPHS9)
Identifiers:: MONDO: MONDO:0014257; MedGen: C3809965; Orphanet: 656; OMIM: 615573

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000109559	OMIM	no assertion criteria provided	Pathogenic (Dec 2, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000494108	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000863832	Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare	no assertion criteria provided	Pathogenic (Mar 13, 2018)	germline	clinical testing
SCV001133137	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	no assertion criteria provided	Likely pathogenic (Sep 26, 2019)	germline	clinical testing
SCV001520809	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002019709	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 12, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004218435	Precision Medicine Center, Zhengzhou University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 1, 2023)	paternal	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24270420, 25741868
SCV004804794	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 17, 2024)	germline	research	PubMed (1) [See all records that cite this PMID]

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	literature only
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, literature only, research
not provided	paternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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

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

Details of each submission

From OMIM, SCV000109559.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 sibs, born of consanguineous Arab parents, with nephrotic syndrome type 9 (NPHS9; 615573), Ashraf et al. (2013) identified a homozygous c.532C-T transition in exon 7 of the ADCK4 gene, resulting in an arg178-to-trp (R178W) substitution at a highly conserved residue. The mutation was found by homozygosity mapping combined with whole-exome sequencing and segregated with the disorder in the family. It was not present in over 190 ethnically matched controls or in the Exome Variant Server database. Functional studies were not performed. The patients had onset of steroid-resistant nephrotic syndrome at ages 7 and 13 years, respectively, and underwent renal transplantation at ages 10 and 15 years, respectively.

#	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 GeneReviews, SCV000494108.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	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 Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare, SCV000863832.1

#	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 Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, SCV001133137.1

#	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 Baylor Genetics, SCV001520809.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002019709.3

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Precision Medicine Center, Zhengzhou University, SCV004218435.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

PM2_p,PM3_strong,PP3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004804794.2

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

#	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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