ClinVar Genomic variation as it relates to human health
NM_000035.4(ALDOB):c.113-1_115del
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.113-1_115del
Variation ID: 188974 Accession: VCV000188974.16
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 9q31.1 9: 101429964-101429967 (GRCh38) [ NCBI UCSC ] 9: 104192246-104192249 (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 29, 2015 Jun 17, 2024 Mar 24, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000035.4:c.113-1_115del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_000035.3:c.113-1_115delGGTA NC_000009.12:g.101429966_101429969del NC_000009.11:g.104192248_104192251del NG_012387.1:g.10814_10817del LRG_1244:g.10814_10817del LRG_1244t1:c.113-1_115del - Protein change
- Other names
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- Canonical SPDI
- NC_000009.12:101429963:TACCTA:TA
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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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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 |
520 | 560 |
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
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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 (6) |
criteria provided, multiple submitters, no conflicts
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Mar 24, 2024 | RCV000169352.16 |
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
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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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Likely pathogenic
(Sep 23, 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: SCV000220722.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Likely pathogenic
(Jan 08, 2023)
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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: SCV000918413.3
First in ClinVar: Jun 02, 2019 Last updated: Nov 11, 2023 |
Comment:
Variant summary: ALDOB c.113-1_115delGGTA is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Variant summary: ALDOB c.113-1_115delGGTA is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 250930 control chromosomes. c.113-1_115delGGTA has been reported in the literature as a homozygous or compound heterozygous genotype in at-least two individuals affected with Hereditary Fructose Intolerance and subsequently cited by others (example, Cross_1990, Ali_1998, Kaiser_1991). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
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Pathogenic
(Feb 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary fructosuria
Affected status: yes
Allele origin:
unknown
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3billion
Accession: SCV003841990.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). This variant was predicted to alter splicing … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). This variant was predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (PMID: 2349937). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Abnormality of the liver (present) , Hepatic steatosis (present) , Autoimmunity (present) , Thyroiditis (present)
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Pathogenic
(Jan 21, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001225800.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This variant results in the deletion of part of exon 3 (c.113-1_115del) of the ALDOB gene. It is expected to disrupt RNA splicing. Variants that … (more)
This variant results in the deletion of part of exon 3 (c.113-1_115del) of the ALDOB gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ALDOB are known to be pathogenic (PMID: 18541450). This variant is present in population databases (rs786204598, gnomAD 0.002%). This variant has been observed in individuals with fructose intolerance (PMID: 2349937, 15880727). ClinVar contains an entry for this variant (Variation ID: 188974). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 24, 2024)
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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: SCV001163211.2
First in ClinVar: Feb 29, 2020 Last updated: Jun 17, 2024 |
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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: SCV001573863.1
First in ClinVar: May 10, 2021 Last updated: May 10, 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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Molecular and clinical findings of Turkish patients with hereditary fructose intolerance. | Gunduz M | Journal of pediatric endocrinology & metabolism : JPEM | 2021 | PMID: 34162028 |
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 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe. | Santer R | Human mutation | 2005 | PMID: 15880727 |
Hereditary fructose intolerance. | Ali M | Journal of medical genetics | 1998 | PMID: 9610797 |
Case report: heterogeneity of aldolase B in hereditary fructose intolerance. | Kaiser UB | The American journal of the medical sciences | 1991 | PMID: 1772121 |
Partial aldolase B gene deletions in hereditary fructose intolerance. | Cross NC | American journal of human genetics | 1990 | PMID: 2349937 |
Text-mined citations for rs786204598 ...
HelpRecord last updated Sep 29, 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.