ClinVar Genomic variation as it relates to human health
NM_014251.3(SLC25A13):c.1638_1660dup (p.Ala554fs)
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_014251.3(SLC25A13):c.1638_1660dup (p.Ala554fs)
Variation ID: 6003 Accession: VCV000006003.50
- Type and length
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Duplication, 23 bp
- Location
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Cytogenetic: 7q21.3 7: 96121928-96121929 (GRCh38) [ NCBI UCSC ] 7: 95751240-95751241 (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 4, 2013 Oct 8, 2024 Mar 28, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_014251.3:c.1638_1660dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055066.1:p.Ala554fs frameshift NM_001160210.2:c.1641_1663dup NP_001153682.1:p.Ala555fs frameshift NM_014251.2:c.1638_1660dup23 NR_027662.2:n.1664_1686dup non-coding transcript variant NC_000007.14:g.96121929_96121951dup NC_000007.13:g.95751241_95751263dup NG_012247.2:g.205197_205219dup - Protein change
- A555fs, A554fs
- Other names
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1638ins23
p.Ala554Glyfs*17
- Canonical SPDI
- NC_000007.14:96121928:CCCGGGCAGCCACCTGTAATCTC:CCCGGGCAGCCACCTGTAATCTCCCCGGGCAGCCACCTGTAATCTC
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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
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The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00009
The Genome Aggregation Database (gnomAD), exomes 0.00009
- 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
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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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SLC25A13 | - | - |
GRCh38 GRCh37 |
844 | 890 |
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 (2) |
criteria provided, single submitter
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Feb 24, 2023 | RCV000006371.8 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Aug 11, 2022 | RCV000726889.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 29, 2024 | RCV000822371.8 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jun 30, 2022 | RCV001004526.7 | |
Pathogenic (2) |
criteria provided, single submitter
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Mar 28, 2024 | RCV002259302.4 | |
SLC25A13-related disorder
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Pathogenic (1) |
no assertion criteria provided
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Mar 22, 2024 | RCV004742217.1 |
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
(-)
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criteria provided, single submitter
Method: clinical testing
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Neonatal intrahepatic cholestasis due to citrin deficiency
Affected status: unknown
Allele origin:
germline
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Baylor Genetics
Accession: SCV001163572.1
First in ClinVar: Feb 29, 2020 Last updated: Feb 29, 2020 |
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Pathogenic
(Feb 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Citrullinemia type II
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003845174.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
Variant summary: SLC25A13 c.1638_1660dup23 (p.Ala554GlyfsX17) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: SLC25A13 c.1638_1660dup23 (p.Ala554GlyfsX17) 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. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.1799dup [p.Tyr600Ter], c.1813C>T [p.Arg605Ter]). The variant allele was found at a frequency of 8.8e-05 in 251412 control chromosomes (gnomAD), predominantly at a frequency of 0.0012 within the East Asian subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in SLC25A13 causing Citrullinemia Type II (8.8e-05 vs 0.0012), allowing no conclusion about variant significance. c.1638_1660dup23 has been reported in the literature as a biallelic genotype in multiple individuals affected with Citrullinemia (e.g. Song_2011, Wang_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters have assessed the variant since 2014: all four classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(May 10, 2021)
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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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Revvity Omics, Revvity
Accession: SCV002020659.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Nov 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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Eurofins Ntd Llc (ga)
Accession: SCV000703906.2
First in ClinVar: Apr 02, 2018 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 3
Sex: mixed
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Pathogenic
(Jun 30, 2022)
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criteria provided, single submitter
Method: clinical testing
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Neonatal intrahepatic cholestasis due to citrin deficiency
Affected status: yes
Allele origin:
germline
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Genesolutions, Medical Genetics Institutes, Ho Chi Minh City, Vietnam
Additional submitter:
Hepatology Department, National Children’s Hospital
Accession: SCV002546529.2
First in ClinVar: Jan 07, 2023 Last updated: Feb 25, 2023 |
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Pathogenic
(Aug 11, 2022)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226563.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PM2, PM3_strong, PVS1
Number of individuals with the variant: 1
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Pathogenic
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Citrin deficiency
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000963171.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ala554Glyfs*17) in the SLC25A13 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ala554Glyfs*17) in the SLC25A13 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC25A13 are known to be pathogenic (PMID: 10369257, 14680984, 27405544). This variant is present in population databases (rs80338725, gnomAD 0.1%). This premature translational stop signal has been observed in individuals with SLC25A13-related conditions (PMID: 27405544). ClinVar contains an entry for this variant (Variation ID: 6003). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 28, 2024)
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criteria provided, single submitter
Method: clinical testing
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Citrullinemia, type II, adult-onset
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004203613.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Jun 01, 1999)
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no assertion criteria provided
Method: literature only
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CITRULLINEMIA, TYPE II, ADULT-ONSET
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000026553.2
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2013 |
Comment on evidence:
In a patient with adult-onset type II citrullinemia (603471), Kobayashi et al. (1999) identified a 23-bp homozygous insertion in exon 16 of SLC25A13, 1638ins23, resulting … (more)
In a patient with adult-onset type II citrullinemia (603471), Kobayashi et al. (1999) identified a 23-bp homozygous insertion in exon 16 of SLC25A13, 1638ins23, resulting in a frameshift at codon 554 and the addition of 16 new amino acids. A stop codon was introduced at position 570, leading to premature termination of the C terminus of citrin. The inserted sequence was apparently a tandem repeat of 23 bp from nucleotide 1638-1660 of SLC25A13 cDNA. (less)
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Pathogenic
(Mar 22, 2024)
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no assertion criteria provided
Method: clinical testing
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SLC25A13-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005353703.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The SLC25A13 c.1638_1660dup23 variant is predicted to result in a frameshift and premature protein termination (p.Ala554Glyfs*17). This variant has been reported in numerous pediatric patients … (more)
The SLC25A13 c.1638_1660dup23 variant is predicted to result in a frameshift and premature protein termination (p.Ala554Glyfs*17). This variant has been reported in numerous pediatric patients with intrahepatic cholestasis with citrin deficiency (Lin WX et al 2016. PubMed ID: 27405544; Nguyen MT et al 2023. PubMed ID: 36599957; Wang NL et al 2019. PubMed ID: 31450232; Song YZ et al 2011. PubMed ID: 21424115) and patients with adult-onset type II citrullinemia (Kobayashi K et al 1999. PubMed ID: 10369257). This variant is almost always reported in a compound heterozygous state with another variant within SLC25A13 (Lin WX et al 2016. PubMed ID: 27405544; Song YZ et al 2011. PubMed ID: 21424115; Wang NL et al 2019. PubMed ID: 31450232), and has been reported in 4 homozygotes as well (Wang NL et al 2019. PubMed ID: 31450232). This variant is reported in 0.12% of alleles in individuals of East Asian descent in gnomAD. Frameshift variants in SLC25A13 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Neonatal intrahepatic cholestasis due to citrin deficiency
Affected status: yes
Allele origin:
germline
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Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital
Accession: SCV004800859.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
PVS1+PM3_VS+PP4
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: Miao
Geographic origin: China
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not provided
(-)
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no classification provided
Method: literature only
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Citrullinemia, type II, adult-onset
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000041254.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
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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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The mutation spectrum of SLC25A13 gene in citrin deficiency: identification of novel mutations in Vietnamese pediatric cohort with neonatal intrahepatic cholestasis. | Nguyen MT | Journal of human genetics | 2023 | PMID: 36599957 |
Molecular epidemiologic study of citrin deficiency by screening for four reported pathogenic SLC25A13 variants in the Shaanxi and Guangdong provinces, China. | Lin WX | Translational pediatrics | 2021 | PMID: 34295780 |
Molecular findings in children with inherited intrahepatic cholestasis. | Wang NL | Pediatric research | 2020 | PMID: 31450232 |
[Analysis of SLC25A13 gene mutations and prenatal diagnosis for 20 families affected with citrin deficiency]. | Shi S | Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics | 2018 | PMID: 30098237 |
Citrin Deficiency. | Adam MP | - | 2017 | PMID: 20301360 |
Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution. | Lin WX | Scientific reports | 2016 | PMID: 27405544 |
Different regional distribution of SLC25A13 mutations in Chinese patients with neonatal intrahepatic cholestasis. | Chen R | World journal of gastroenterology | 2013 | PMID: 23901231 |
Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among Thai infants. | Treepongkaruna S | BMC gastroenterology | 2012 | PMID: 23067347 |
Genotypic and phenotypic features of citrin deficiency: five-year experience in a Chinese pediatric center. | Song YZ | International journal of molecular medicine | 2011 | PMID: 21424115 |
The mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and aminoacidemia. | Fu HY | Journal of gastroenterology | 2011 | PMID: 20927635 |
Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor. | Shigeta T | Pediatric transplantation | 2010 | PMID: 19413723 |
Screening of nine SLC25A13 mutations: their frequency in patients with citrin deficiency and high carrier rates in Asian populations. | Kobayashi K | Molecular genetics and metabolism | 2003 | PMID: 14680984 |
A Chinese adult onset type II citrullinaemia patient with 851del4/1638ins23 mutations in the SLC25A13 gene. | Hwu WL | Journal of medical genetics | 2001 | PMID: 11432966 |
The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. | Kobayashi K | Nature genetics | 1999 | PMID: 10369257 |
A search for the primary abnormality in adult-onset type II citrullinemia. | Kobayashi K | American journal of human genetics | 1993 | PMID: 8105687 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC25A13 | - | - | - | - |
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Text-mined citations for rs80338725 ...
HelpRecord last updated Oct 13, 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.