ClinVar Genomic variation as it relates to human health
NM_000387.6(SLC25A20):c.199-10T>G
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_000387.6(SLC25A20):c.199-10T>G
Variation ID: 12137 Accession: VCV000012137.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p21.31 3: 48884134 (GRCh38) [ NCBI UCSC ] 3: 48921567 (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 Apr 27, 2014 Oct 8, 2024 Mar 27, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000387.6:c.199-10T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NC_000003.12:g.48884134A>C NC_000003.11:g.48921567A>C NG_008171.1:g.19763T>G - Protein change
- Other names
- IVS2AS, T-G, -10
- Canonical SPDI
- NC_000003.12:48884133:A:C
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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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0.00020 (C)
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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00007
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
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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SLC25A20 | - | - |
GRCh38 GRCh37 |
306 | 320 |
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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Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Mar 27, 2024 | RCV000012920.19 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 18, 2021 | RCV000427395.5 | |
SLC25A20-related disorder
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Pathogenic (1) |
no assertion criteria provided
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Jul 23, 2024 | RCV004757104.1 |
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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Pathogenic
(Jan 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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Carnitine acylcarnitine translocase deficiency
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000632619.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024 |
Comment:
This sequence change falls in intron 2 of the SLC25A20 gene. It does not directly change the encoded amino acid sequence of the SLC25A20 protein. … (more)
This sequence change falls in intron 2 of the SLC25A20 gene. It does not directly change the encoded amino acid sequence of the SLC25A20 protein. This variant is present in population databases (rs541208710, gnomAD 0.09%). This variant has been observed in individuals with carnitine–acylcarnitine translocase deficiency (PMID: 10697964, 24088670, 25459972, 26238931, 27066551). It has also been observed to segregate with disease in related individuals. This variant is also known as 261-10T>G. ClinVar contains an entry for this variant (Variation ID: 12137). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 27, 2024)
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criteria provided, single submitter
Method: clinical testing
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Carnitine acylcarnitine translocase deficiency
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004201707.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Nov 18, 2021)
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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: SCV000515900.6
First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023 |
Comment:
Reverse transcriptase PCR in patient fibroblasts indicate c.199-10 T>G results in abnormal gene splicing (Ogawa et al., 2000); This variant is associated with the following … (more)
Reverse transcriptase PCR in patient fibroblasts indicate c.199-10 T>G results in abnormal gene splicing (Ogawa et al., 2000); This variant is associated with the following publications: (PMID: 25459972, 29137068, 10697964, 15363639, 11592821, 29996190, 31108048, 31965297, 31501239, 32411386, 33634872, 33194920, 32778825, 24088670) (less)
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Pathogenic
(Jan 06, 2017)
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criteria provided, single submitter
Method: clinical testing
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Carnitine acylcarnitine translocase deficiency
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696660.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
Variant summary: The SLC25A20 c.199-10T>G variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a disease-causing outcome for this variant. … (more)
Variant summary: The SLC25A20 c.199-10T>G variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a disease-causing outcome for this variant. 5/5 splice prediction tools predict the creation or enhancement of a cryptic splice donor site along with the weakening of a canonical splicing acceptor site. Functional studies have shown the patients with this variant in compound heterozygosity had exon 3/4 skipping, and abberant splicing was also observed in patients and parents who had coding variants suggesting coding sequence mutations might contribute to the presence of aberrantly spliced mRNA (Hsu_2001). The variant was found in numerous affected individuals both in the homozygous and heterozygous state, and the variant has been suggested as an Asian founder mutation. This variant was found in 4/121236 control chromosomes at a frequency of 0.000033, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC25A20 variant (0.001118). In addition, one reputable clinical diagnostic laboratory/multiple reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(May 10, 2019)
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criteria provided, single submitter
Method: clinical testing
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Carnitine acylcarnitine translocase deficiency
Affected status: yes
Allele origin:
paternal
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Center for Molecular Medicine, Children’s Hospital of Fudan University
Accession: SCV001190562.1
First in ClinVar: Mar 29, 2020 Last updated: Mar 29, 2020 |
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Pathogenic
(Mar 26, 2020)
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criteria provided, single submitter
Method: clinical testing
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Carnitine acylcarnitine translocase deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556627.2
First in ClinVar: Aug 04, 2022 Last updated: Dec 17, 2022 |
Comment:
The SLC25A20:c.199-10T>G variant is a single nucleotide substitution which results in aberrant splicing. The variant has been reported in the literature as homozygous or heterozygous … (more)
The SLC25A20:c.199-10T>G variant is a single nucleotide substitution which results in aberrant splicing. The variant has been reported in the literature as homozygous or heterozygous in combination with another SLC25A20 variant in affected patients (PMID: 25459972, PMID: 25459972) . It has been described as a founder mutation in East Asian populations. RNA studies demonstrate exon 3 and exon 3/4 skipping which is predicted to be detrimental to protein function (PMID: 10697964). It is present in population databases at 0.007% (20 het/280674 allele count) (PP). Splice prediction programs in Alamut indicate that the variant may disrupt the exon 3 acceptor site. The variant is described in ClinVar as pathogenic and HGMD (2019.4) as disease causing (PP5). (less)
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Pathogenic
(Dec 01, 2013)
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no assertion criteria provided
Method: literature only
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CARNITINE-ACYLCARNITINE TRANSLOCASE DEFICIENCY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000033161.3
First in ClinVar: Apr 04, 2013 Last updated: Aug 09, 2019 |
Comment on evidence:
In a patient with CACT deficiency (CACTD; 212138), Ogawa et al. (2000) found compound heterozygosity for a splice site mutation, a T-to-G transversion at the … (more)
In a patient with CACT deficiency (CACTD; 212138), Ogawa et al. (2000) found compound heterozygosity for a splice site mutation, a T-to-G transversion at the nucleotide -10 upstream from the splice acceptor site of intron 2, and a 146delT mutation (613698.0005). In a Japanese patient who died of CACT deficiency, Fukushima et al. (2013) identified compound heterozygous mutations in the SLC25A20 gene: a T-to-G transversion in intron 2 (c.199-10T-G) and W192X (613698.0008). Each unaffected parent was heterozygous for 1 of the mutations. (less)
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Pathogenic
(Jul 23, 2024)
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no assertion criteria provided
Method: clinical testing
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SLC25A20-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005358930.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The SLC25A20 c.199-10T>G variant is predicted to interfere with splicing. This variant has been reported in the compound heterozygous and homozygous state in multiple patients … (more)
The SLC25A20 c.199-10T>G variant is predicted to interfere with splicing. This variant has been reported in the compound heterozygous and homozygous state in multiple patients with autosomal recessive carnitine-acylcarnitine translocase deficiency (Ogawa et al. 2000. PubMed ID: 10697964, Tang et al. 2019. PubMed ID: 31108048, Vatanavicharn et al. 2015. PubMed ID: 25459972). RNA studies showed that this variant leads to aberrant splicing and truncation of the protein (Ogawa et al. 2000. PubMed ID: 10697964). This variant is reported in 0.095% of alleles in individuals of East Asian descent in gnomAD. This variant is interpreted as pathogenic. (less)
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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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Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS. | Tian X | Neurology. Genetics | 2015 | PMID: 27066551 |
SSIEM 2015 Annual Symposium : Lyon, France, August 2015. | - | Journal of inherited metabolic disease | 2015 | PMID: 26238931 |
Carnitine-acylcarnitine translocase deficiency: Two neonatal cases with common splicing mutation and in vitro bezafibrate response. | Vatanavicharn N | Brain & development | 2015 | PMID: 25459972 |
Three novel mutations in the carnitine-acylcarnitine translocase (CACT) gene in patients with CACT deficiency and in healthy individuals. | Fukushima T | Journal of human genetics | 2013 | PMID: 24088670 |
Carnitine-acylcarnitine translocase deficiency in three neonates presenting with rapid deterioration and cardiac arrest. | Lee RS | Hong Kong medical journal = Xianggang yi xue za zhi | 2007 | PMID: 17277394 |
Mutational spectrum and DNA-based prenatal diagnosis in carnitine-acylcarnitine translocase deficiency. | Costa C | Molecular genetics and metabolism | 2003 | PMID: 12559850 |
Aberrant mRNA splicing associated with coding region mutations in children with carnitine-acylcarnitine translocase deficiency. | Hsu BY | Molecular genetics and metabolism | 2001 | PMID: 11592821 |
Identification of two novel mutations of the carnitine/acylcarnitine translocase (CACT) gene in a patient with CACT deficiency. | Ogawa A | Journal of human genetics | 2000 | PMID: 10697964 |
Text-mined citations for rs541208710 ...
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.