ClinVar Genomic variation as it relates to human health
NM_003060.4(SLC22A5):c.391G>A (p.Glu131Lys)
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.391G>A (p.Glu131Lys)
Variation ID: 1429538 Accession: VCV001429538.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q31.1 5: 132370363 (GRCh38) [ NCBI UCSC ] 5: 131706055 (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 Mar 28, 2022 Oct 8, 2024 Jun 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003060.4:c.391G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003051.1:p.Glu131Lys missense NM_001308122.2:c.391G>A NP_001295051.1:p.Glu131Lys missense NM_003060.3:c.391G>A NC_000005.10:g.132370363G>A NC_000005.9:g.131706055G>A NG_008982.2:g.5660G>A - Protein change
- E131K
- Other names
- p.Glu131Lys
- Canonical SPDI
- NC_000005.10:132370362:G: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) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
- 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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SLC22A5 | - | - |
GRCh38 GRCh37 |
1174 | 1217 |
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 | RCV001938987.8 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Jun 1, 2024 | RCV003107900.7 |
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
(Oct 03, 2022)
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criteria provided, single submitter
Method: research, in vitro
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Renal carnitine transport defect
Affected status: not applicable, unknown
Allele origin:
germline,
not applicable
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Giacomini Lab, University of California, San Francisco
Accession: SCV002576670.1
First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022 |
Observation 1: Observation 2:
Method: In vitro uptake assays in HEK293T cells transiently expressing the variant were used to measure variant function relative to the reference allele. Function is reported as a % of the wild-type (reference) SLC22A5/OCTN2 transporter with respect to uptake of C14-carnitine.
Result:
The variant has 27.2% function of the wild-type SLC22A5/OCTN2 transporter with respect to transport of C14-carnitine in vitro.
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Uncertain significance
(Nov 13, 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:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002816639.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Aug 09, 2022)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002200628.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 131 of the SLC22A5 protein … (more)
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 131 of the SLC22A5 protein (p.Glu131Lys). 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 variant has not been reported in the literature in individuals affected with SLC22A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1429538). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Jan 25, 2023)
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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: SCV003761757.2
First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023 |
Comment:
Described as a non deleterious variant, with functional studies of carnitine uptake by OCNT2 in transfected cells showing no significant difference compared to wildtype (Rodin … (more)
Described as a non deleterious variant, with functional studies of carnitine uptake by OCNT2 in transfected cells showing no significant difference compared to wildtype (Rodin M et al., 2020); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: Rdin2020[DegreeProject]) (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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Carnitine deficiency, systemic primary
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV005016525.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
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Uncertain significance
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005188588.1
First in ClinVar: Aug 18, 2024 Last updated: Aug 18, 2024 |
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Uncertain significance
(Jun 01, 2024)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV005075097.3
First in ClinVar: Jul 15, 2024 Last updated: Oct 08, 2024 |
Comment:
SLC22A5: PM2, PP3
Number of individuals with the variant: 1
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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs1321705165 ...
HelpRecord last updated Oct 08, 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.