ClinVar Genomic variation as it relates to human health
NM_023936.2(MRPS34):c.94C>T (p.Gln32Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_023936.2(MRPS34):c.94C>T (p.Gln32Ter)
Variation ID: 438635 Accession: VCV000438635.49
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 16p13.3 16: 1773026 (GRCh38) [ NCBI UCSC ] 16: 1823027 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Sep 19, 2017 Aug 25, 2024 Mar 6, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_023936.2:c.94C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_076425.1:p.Gln32Ter nonsense NM_001300900.2:c.94C>T NP_001287829.1:p.Gln32Ter nonsense NC_000016.10:g.1773026G>A NC_000016.9:g.1823027G>A - Protein change
- Q32*
- Other names
- MRPS34, GLN32TER (rs763672163)
- NM_001300900.1:c.94C>T(p.Gln32Ter)
- NM_023936.1:c.94C>T(p.Gln32Ter)
- Canonical SPDI
- NC_000016.10:1773025:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00016
The Genome Aggregation Database (gnomAD), exomes 0.00044
Trans-Omics for Precision Medicine (TOPMed) 0.00070
The Genome Aggregation Database (gnomAD) 0.00071
Exome Aggregation Consortium (ExAC) 0.00340
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
EME2 | - | - |
GRCh38 GRCh37 |
5 | 145 | |
MRPS34 | - | - |
GRCh38 GRCh37 |
43 | 159 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
|
Mar 6, 2024 | RCV000505531.16 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 22, 2024 | RCV000760555.31 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Likely pathogenic
(Apr 16, 2018)
|
criteria provided, single submitter
Method: curation
|
Combined oxidative phosphorylation deficiency 32
Affected status: unknown
Allele origin:
germline
|
SIB Swiss Institute of Bioinformatics
Accession: SCV000787467.1
First in ClinVar: Jul 21, 2018 Last updated: Jul 21, 2018 |
Comment:
This variant is interpreted as a Likely Pathogenic, for Combined oxidative phosphorylation deficiency 32, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PP3 => … (more)
This variant is interpreted as a Likely Pathogenic, for Combined oxidative phosphorylation deficiency 32, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3 => Well-established functional studies show a deleterious effect. PM3-Supporting => PM3 downgraded in strength to Supporting (PMID:28777931). (less)
|
|
Pathogenic
(Sep 27, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Combined oxidative phosphorylation deficiency 32
Affected status: yes
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV001524838.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as pathogenic [PMID: 28777931, ClinVar ID: … (more)
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as pathogenic [PMID: 28777931, ClinVar ID: 438635] (less)
|
|
Likely pathogenic
(May 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Combined oxidative phosphorylation deficiency 32
Affected status: yes
Allele origin:
germline
|
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002061558.2
First in ClinVar: Jan 22, 2022 Last updated: Feb 11, 2022 |
Comment:
PVS1, PM3
|
|
Pathogenic
(Jan 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Combined oxidative phosphorylation deficiency 32
Affected status: yes
Allele origin:
maternal
|
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues
Accession: SCV002320736.1
First in ClinVar: Apr 08, 2022 Last updated: Apr 08, 2022 |
|
|
Pathogenic
(Sep 16, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000890446.7
First in ClinVar: Mar 19, 2019 Last updated: Sep 30, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28777931, 30358850, 30566640, 35326425, 37385809) (less)
|
|
Likely pathogenic
(Jan 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Combined oxidative phosphorylation deficiency 32
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002023518.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Jan 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001208611.3
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln32*) in the MRPS34 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln32*) in the MRPS34 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MRPS34 are known to be pathogenic (PMID: 28777931). This variant is present in population databases (rs763672163, gnomAD 0.1%). This premature translational stop signal has been observed in individuals with Leigh syndrome, transient metabolic acidosis and hemodynamic instability related to tubulopathy (PMID: 28777931). ClinVar contains an entry for this variant (Variation ID: 438635). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Likely pathogenic
(Nov 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001149646.25
First in ClinVar: Feb 03, 2020 Last updated: Aug 04, 2024 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Oct 19, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Combined oxidative phosphorylation deficiency 32
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002767779.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with combined oxidative phosphorylation deficiency 32 (MIM#61766). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD v3 <0.01 for a recessive condition (100 heterozygotes, 0 homozygotes). (SP) 0705 - No comparable NMD-predicted variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported multiple times as pathogenic or likely pathogenic (ClinVar, LOVD) and has been reported in a single compound heterozygous patient with Leigh's syndrome (PMID: 28777931). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Functional studies on patient cells found this variant resulted in reduced OXPHOS levels, mitochondrial protein translation and mitochondrial subunit proteins. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
|
Pathogenic
(Mar 06, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Combined oxidative phosphorylation deficiency 32
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002572006.2
First in ClinVar: Sep 17, 2022 Last updated: Jun 29, 2024 |
Comment:
Variant summary: MRPS34 c.94C>T (p.Gln32X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: MRPS34 c.94C>T (p.Gln32X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.00044 in 52648 control chromosomes (gnomAD). c.94C>T has been reported in the literature in individuals affected with Combined Oxidative Phosphorylation Deficiency 32 or Leigh syndrome (Lake_2017, Shen_2023). Western blot analysis using fibroblasts from one patient showed a significant reduction in the MRPS34 protein, as well as reduction in complexes CI and CIV (Lake_2017). The following publications have been ascertained in the context of this evaluation (PMID: 28777931, 35326425, 37385809). ClinVar contains an entry for this variant (Variation ID: 438635). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
Pathogenic
(May 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199168.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
|
|
Pathogenic
(Sep 15, 2017)
|
no assertion criteria provided
Method: literature only
|
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 32
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000599787.1
First in ClinVar: Sep 19, 2017 Last updated: Sep 19, 2017 |
Comment on evidence:
For discussion of the c.94C-T transition (c.94C-T, NM_023936.1) in the MRPS34 gene, resulting in a gln32-to-ter (Q32X) substitution, that was found in compound heterozygous state … (more)
For discussion of the c.94C-T transition (c.94C-T, NM_023936.1) in the MRPS34 gene, resulting in a gln32-to-ter (Q32X) substitution, that was found in compound heterozygous state in a patient with combined oxidative phosphorylation deficiency-32 (COXPD32; 617664) by Lake et al. (2017), see 611994.0003. (less)
|
|
click to load more click to collapse |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
[A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review]. | Shen MX | Zhonghua er ke za zhi = Chinese journal of pediatrics | 2023 | PMID: 37385809 |
Biallelic Variants in ENDOG Associated with Mitochondrial Myopathy and Multiple mtDNA Deletions. | Nasca A | Cells | 2022 | PMID: 35326425 |
Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome. | Lake NJ | American journal of human genetics | 2017 | PMID: 28777931 |
Text-mined citations for rs763672163 ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.