ClinVar Genomic variation as it relates to human health
NM_003060.4(SLC22A5):c.807A>G (p.Leu269=)
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_003060.4(SLC22A5):c.807A>G (p.Leu269=)
Variation ID: 94101 Accession: VCV000094101.34
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q31.1 5: 132385482 (GRCh38) [ NCBI UCSC ] 5: 131721174 (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 Dec 6, 2016 Feb 20, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003060.4:c.807A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003051.1:p.Leu269= synonymous NM_001308122.2:c.879A>G NP_001295051.1:p.Leu293= synonymous NC_000005.10:g.132385482A>G NC_000005.9:g.131721174A>G NG_008982.2:g.20779A>G - Protein change
- Other names
- -
- Canonical SPDI
- NC_000005.10:132385481:A:G
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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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0.48622 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.37829
Trans-Omics for Precision Medicine (TOPMed) 0.38465
The Genome Aggregation Database (gnomAD) 0.39440
1000 Genomes Project 30x 0.47564
1000 Genomes Project 0.48622
The Genome Aggregation Database (gnomAD), exomes 0.43520
Exome Aggregation Consortium (ExAC) 0.43925
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
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. |
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SLC22A5 | - | - |
GRCh38 GRCh37 |
1155 | 1197 |
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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Benign (3) |
criteria provided, single submitter
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Dec 7, 2017 | RCV000080060.14 | |
Benign (7) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000402674.23 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Apr 18, 2016 | RCV000587609.4 |
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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Benign
(Aug 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Renal carnitine transport defect
Affected status: unknown
Allele origin:
germline
|
Phosphorus, Inc.
Accession: SCV000679883.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 13
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Benign
(Apr 18, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698157.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The c.807A>G variant affects a non-conserved nucleotide, resulting in synonymous amino acid change. Mutatation Taster predicts polymorphism outcome for this variant. 5/5 splice-site … (more)
Variant summary: The c.807A>G variant affects a non-conserved nucleotide, resulting in synonymous amino acid change. Mutatation Taster predicts polymorphism outcome for this variant. 5/5 splice-site tools via Alamut predict that this variant does not affect the consensus splice donor site though it may create a cryptic splice donor site as predicted by 3/5 tools. However, in silico prediction results are not definite and there are no functional studies to confirm this. This variant is found in 53257/121244 control chromosomes (12476 homozygotes) from the large and broad populations of ExAC at a frequency of 0.4392547, which is about 96 times greater than the maximal expected frequency of a pathogenic allele (0.0045644) in this gene. Thus this variant is a common polymorphism found in general population. In one family, this variant was found in cis with a potentially pathogenic variant p.Leu476Arg in homozygous state in two affected siblings and was found in homozygous state in the unaffected father of the siblings (Mutlu-Albayrak_2015) -- an evidence of lack of cosegregation which further supports the benign outcome. One clinical laboratory has classified this variant as benign. Taken together, this variant has been classified as Benign. (less)
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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Renal carnitine transport defect
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000452732.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(Jun 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Renal carnitine transport defect
Affected status: no
Allele origin:
germline
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Pars Genome Lab
Accession: SCV001738691.1
First in ClinVar: Jun 26, 2021 Last updated: Jun 26, 2021 |
Sex: mixed
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Benign
(Mar 03, 2015)
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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: SCV001834234.1
First in ClinVar: Sep 12, 2021 Last updated: Sep 12, 2021 |
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Benign
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Renal carnitine transport defect
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002055873.1
First in ClinVar: Jan 11, 2022 Last updated: Jan 11, 2022 |
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Benign
(Dec 07, 2017)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000111955.8
First in ClinVar: Jan 17, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 82
Sex: mixed
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Benign
(Oct 20, 2021)
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criteria provided, single submitter
Method: clinical testing
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Renal carnitine transport defect
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000605129.4
First in ClinVar: Dec 06, 2016 Last updated: Jan 08, 2022 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Renal carnitine transport defect
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001728989.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
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Benign
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Primary systemic carnitine deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001462811.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001744248.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001951659.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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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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Identification of SLC22A5 Gene Mutation in a Family with Carnitine Uptake Defect. | Mutlu-Albayrak H | Case reports in genetics | 2015 | PMID: 26075114 |
Free the data: one laboratory's approach to knowledge-based genomic variant classification and preparation for EMR integration of genomic data. | Bean LJ | Human mutation | 2013 | PMID: 23757202 |
Genetic variations of the SLC22A5 gene in the Chinese and Indian populations of Singapore. | Toh DS | Drug metabolism and pharmacokinetics | 2010 | PMID: 20208395 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC22A5 | - | - | - | - |
Text-mined citations for rs274558 ...
HelpRecord last updated Feb 28, 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.