ClinVar Genomic variation as it relates to human health
NM_024120.5(NDUFAF5):c.821T>A (p.Leu274Gln)
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
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NM_024120.5(NDUFAF5):c.821T>A (p.Leu274Gln)
Variation ID: 800896 Accession: VCV000800896.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20p12.1 20: 13816505 (GRCh38) [ NCBI UCSC ] 20: 13797151 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jan 4, 2020 May 1, 2024 Mar 14, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024120.5:c.821T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_077025.2:p.Leu274Gln missense NM_001039375.3:c.737T>A NP_001034464.1:p.Leu246Gln missense NM_001352403.2:c.350T>A NP_001339332.1:p.Leu117Gln missense NM_001352406.2:c.260T>A NP_001339335.1:p.Leu87Gln missense NM_001352407.2:c.260T>A NP_001339336.1:p.Leu87Gln missense NR_029377.2:n.960T>A non-coding transcript variant NR_147978.2:n.918T>A non-coding transcript variant NR_147979.2:n.980T>A non-coding transcript variant NR_147980.2:n.856T>A non-coding transcript variant NR_147981.2:n.1094T>A non-coding transcript variant NR_147982.2:n.1150T>A non-coding transcript variant NR_147983.2:n.1010T>A non-coding transcript variant NC_000020.11:g.13816505T>A NC_000020.10:g.13797151T>A NG_015811.1:g.36480T>A - Protein change
- L117Q, L87Q, L246Q, L274Q
- Other names
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- Canonical SPDI
- NC_000020.11:13816504:T:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
- Links
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 | ||
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HI score
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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. |
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NDUFAF5 | - | - |
GRCh38 GRCh38 GRCh37 |
390 | 522 |
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. |
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Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Mar 14, 2024 | RCV000985087.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 27, 2019 | RCV001555266.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 24, 2023 | RCV003117659.3 |
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. |
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Uncertain significance
(Sep 24, 2019)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex 1 deficiency, nuclear type 16
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001520719.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
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Uncertain significance
(Aug 27, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001776651.1
First in ClinVar: Aug 14, 2021 Last updated: Aug 14, 2021 |
Comment:
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports … (more)
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31130284, 28454995) (less)
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Uncertain significance
(May 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex 1 deficiency, nuclear type 16
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002778535.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Jan 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003801180.2
First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023 |
Comment:
Variant summary: NDUFAF5 c.821T>A (p.Leu274Gln) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: NDUFAF5 c.821T>A (p.Leu274Gln) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251344 control chromosomes. c.821T>A has been reported in the literature as a homozygous genotype in at-least one individual affected with features of Mitochondrial complex 1 deficiency/Leigh Syndrome, however, the possibility of additional independent homozygous cases or cohort overlap with the primary report in subsequent citations cannot be ruled out (example, PMID: 28454995, 31130284, 34645488). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. (less)
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Uncertain significance
(Mar 14, 2024)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex I deficiency, nuclear type 16
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV005016570.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
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Likely pathogenic
(Sep 26, 2019)
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no assertion criteria provided
Method: clinical testing
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Mitochondrial complex 1 deficiency, nuclear type 16
Affected status: yes
Allele origin:
germline
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Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001133047.1
First in ClinVar: Jan 04, 2020 Last updated: Jan 04, 2020 |
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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 |
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Lethal variants in humans: lessons learned from a large molecular autopsy cohort. | Shamseldin HE | Genome medicine | 2021 | PMID: 34645488 |
Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population. | Monies D | American journal of human genetics | 2019 | PMID: 31130284 |
A multicenter clinical exome study in unselected cohorts from a consanguineous population of Saudi Arabia demonstrated a high diagnostic yield. | Alfares A | Molecular genetics and metabolism | 2017 | PMID: 28454995 |
Text-mined citations for rs1040187200 ...
HelpRecord last updated May 01, 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.