ClinVar Genomic variation as it relates to human health
NM_000035.4(ALDOB):c.178C>T (p.Arg60Ter)
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_000035.4(ALDOB):c.178C>T (p.Arg60Ter)
Variation ID: 472 Accession: VCV000000472.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q31.1 9: 101429901 (GRCh38) [ NCBI UCSC ] 9: 104192183 (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 Feb 14, 2024 Jan 18, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000035.4:c.178C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000026.2:p.Arg60Ter nonsense NC_000009.12:g.101429901G>A NC_000009.11:g.104192183G>A NG_012387.1:g.10880C>T LRG_1244:g.10880C>T LRG_1244t1:c.178C>T LRG_1244p1:p.Arg60Ter - Protein change
- R60*
- Other names
- R59*
- Canonical SPDI
- NC_000009.12:101429900: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
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00008
Exome Aggregation Consortium (ExAC) 0.00009
The Genome Aggregation Database (gnomAD) 0.00010
1000 Genomes Project 30x 0.00031
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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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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ALDOB | - | - |
GRCh38 GRCh37 |
500 | 539 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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/Likely pathogenic (11) |
criteria provided, multiple submitters, no conflicts
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Jan 18, 2024 | RCV000000501.30 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 6, 2022 | RCV000760464.3 | |
Pathogenic (1) |
criteria provided, single submitter
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May 9, 2019 | RCV002251843.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 21, 2022 | RCV002512606.1 | |
Pathogenic (1) |
criteria provided, single submitter
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May 16, 2023 | RCV003407248.4 |
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
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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
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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
(Nov 09, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary fructosuria
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000916436.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: The ALDOB c.178C>T (p.Arg60X) variant results in a premature termination codon, predicted to cause a truncated or absent ALDOB protein due to nonsense … (more)
Variant summary: The ALDOB c.178C>T (p.Arg60X) variant results in a premature termination codon, predicted to cause a truncated or absent ALDOB protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 20/277036 control chromosomes (gnomAD) at a frequency of 0.0000722, which does not exceed the estimated maximal expected allele frequency of a pathogenic ALDOB variant (0.0044721). Multiple publications have cited the variant in affected compound heterozygote and homozygote patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(May 09, 2019)
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criteria provided, single submitter
Method: clinical testing
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See cases
Affected status: yes
Allele origin:
germline
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Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV002523704.1
First in ClinVar: Jun 09, 2022 Last updated: Jun 09, 2022 |
Comment:
ACMG classification criteria: PVS1, PM2, PM3, PP3, PP5
Clinical Features:
Delayed speech and language development (present) , Hypoglycemia (present) , Portal fibrosis (present) , Hepatic steatosis (present)
Geographic origin: Brazil
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Pathogenic
(May 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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ALDOB-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004113432.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The ALDOB c.178C>T variant is predicted to result in premature protein termination (p.Arg60*). This variant has been reported to be causative for hereditary fructose intolerance … (more)
The ALDOB c.178C>T variant is predicted to result in premature protein termination (p.Arg60*). This variant has been reported to be causative for hereditary fructose intolerance (Brooks et al. 1994. PubMed ID: 8299883; Valadares et al. 2015. PubMed ID: 26937407; Reid et al. 2016. PubMed ID: 27604308; Kim et al. 2021. PubMed ID: 33028743). Note, this is also referred to as R59op, Arg59Ter, and Arg60Ter in some literature. This variant is reported in 0.011% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-104192183-G-A). Nonsense variants in ALDOB are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Jan 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary fructosuria
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002024916.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jul 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary fructosuria
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001810254.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Sex: mixed
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Likely pathogenic
(Jun 10, 2014)
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criteria provided, single submitter
Method: literature only
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Hereditary fructosuria
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220395.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Nov 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary fructosuria
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000894462.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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Pathogenic
(Apr 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003528888.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
The c.178C>T (p.R60*) alteration, located in exon 3 (coding exon 2) of the ALDOB gene, consists of a C to T substitution at nucleotide position … (more)
The c.178C>T (p.R60*) alteration, located in exon 3 (coding exon 2) of the ALDOB gene, consists of a C to T substitution at nucleotide position 178. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 60. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.0085% (24/282704) total alleles studied. The highest observed frequency was 0.01% (4/35438) of Latino alleles. This alteration has been reported in multiple patients with hereditary fructose intolerance (Brooks, 1994; Santer, 2005; Davit-Spraul, 2008; Valadares, 2015; Kim, 2021). Based on the available evidence, this alteration is classified as pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(Sep 06, 2022)
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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: SCV000890352.3
First in ClinVar: Mar 19, 2019 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Also … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Also reported as R59X due to alternate nomenclature; This variant is associated with the following publications: (PMID: 25525159, 8299883, 8071980, 26937407, 15880727, 27604308, 20882353, 20033295, 8299892, 35398868, 18541450) (less)
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Pathogenic
(Oct 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary fructosuria
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004196071.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 18, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary fructosuria
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000964566.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg60*) in the ALDOB gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg60*) in the ALDOB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALDOB are known to be pathogenic (PMID: 18541450). This variant is present in population databases (rs118204429, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with hereditary fructose intolerance (PMID: 8071980, 8299883, 15880727, 20882353, 26937407). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 472). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 01, 1994)
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no assertion criteria provided
Method: literature only
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FRUCTOSE INTOLERANCE, HEREDITARY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000020650.2
First in ClinVar: Apr 04, 2013 Last updated: May 04, 2020 |
Comment on evidence:
In an Austrian woman with fructose intolerance (HFI; 229600) who was known to have 1 copy of the East European N334K mutation (612724.0006), Ali et … (more)
In an Austrian woman with fructose intolerance (HFI; 229600) who was known to have 1 copy of the East European N334K mutation (612724.0006), Ali et al. (1994) found that the other allele had a C-to-T transition, resulting in an arg59-to-ter (R59X) substitution. (less)
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Fructose intolerance
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001462846.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Likely pathogenic
(Mar 18, 2021)
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no assertion criteria provided
Method: literature only
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Hereditary fructosuria
Affected status: yes
Allele origin:
unknown
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ATS em Genética Clínica, Universidade Federal do Rio Grande do Sul
Accession: SCV001573831.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Hereditary fructosuria
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000257568.3
First in ClinVar: Dec 24, 2015 Last updated: Oct 01, 2022 |
Comment:
One of the six most common HFI variants in US and European populations including Turkey, Spain, Central Europe, France, US, and Italy
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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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Hereditary Fructose Intolerance Diagnosed in Adulthood. | Kim MS | Gut and liver | 2021 | PMID: 33028743 |
Hereditary Fructose Intolerance. | Adam MP | - | 2021 | PMID: 26677512 |
Hereditary fructose intolerance in Brazilian patients. | Valadares ER | Molecular genetics and metabolism reports | 2015 | PMID: 26937407 |
Integration of PCR-Sequencing Analysis with Multiplex Ligation-Dependent Probe Amplification for Diagnosis of Hereditary Fructose Intolerance. | Ferri L | JIMD reports | 2012 | PMID: 23430936 |
Mutations in the promoter region of the aldolase B gene that cause hereditary fructose intolerance. | Coffee EM | Journal of inherited metabolic disease | 2010 | PMID: 20882353 |
Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population. | Coffee EM | Journal of inherited metabolic disease | 2010 | PMID: 20033295 |
Hereditary fructose intolerance: frequency and spectrum mutations of the aldolase B gene in a large patients cohort from France--identification of eight new mutations. | Davit-Spraul A | Molecular genetics and metabolism | 2008 | PMID: 18541450 |
The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe. | Santer R | Human mutation | 2005 | PMID: 15880727 |
Molecular analysis of the aldolase B gene in patients with hereditary fructose intolerance from Spain. | Sánchez-Gutiérrez JC | Journal of medical genetics | 2002 | PMID: 12205126 |
Mutation analysis in Turkish patients with hereditary fructose intolerance. | Dursun A | Journal of inherited metabolic disease | 2001 | PMID: 11757579 |
Aldolase B and fructose intolerance. | Cox TM | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 1994 | PMID: 8299892 |
A partially active mutant aldolase B from a patient with hereditary fructose intolerance. | Brooks CC | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 1994 | PMID: 8299883 |
Null alleles of the aldolase B gene in patients with hereditary fructose intolerance. | Ali M | Journal of medical genetics | 1994 | PMID: 8071980 |
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Text-mined citations for rs118204429 ...
HelpRecord last updated Mar 17, 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.