rs118204425
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5
The NM_000035.4(ALDOB):c.865_867del(p.Leu289del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
ALDOB
NM_000035.4 inframe_deletion
NM_000035.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.74
Genes affected
ALDOB (HGNC:417): (aldolase, fructose-bisphosphate B) Fructose-1,6-bisphosphate aldolase (EC 4.1.2.13) is a tetrameric glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Vertebrates have 3 aldolase isozymes which are distinguished by their electrophoretic and catalytic properties. Differences indicate that aldolases A, B, and C are distinct proteins, the products of a family of related 'housekeeping' genes exhibiting developmentally regulated expression of the different isozymes. The developing embryo produces aldolase A, which is produced in even greater amounts in adult muscle where it can be as much as 5% of total cellular protein. In adult liver, kidney and intestine, aldolase A expression is repressed and aldolase B is produced. In brain and other nervous tissue, aldolase A and C are expressed about equally. There is a high degree of homology between aldolase A and C. Defects in ALDOB cause hereditary fructose intolerance. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a helix (size 12) in uniprot entity ALDOB_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_000035.4
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_000035.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 9-101424974-AAAG-A is Pathogenic according to our data. Variant chr9-101424974-AAAG-A is described in ClinVar as [Pathogenic]. Clinvar id is 466.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDOB | NM_000035.4 | c.865_867del | p.Leu289del | inframe_deletion | 8/9 | ENST00000647789.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDOB | ENST00000647789.2 | c.865_867del | p.Leu289del | inframe_deletion | 8/9 | NM_000035.4 | P1 | ||
ALDOB | ENST00000648064.1 | c.865_867del | p.Leu289del | inframe_deletion | 8/9 | P1 | |||
ALDOB | ENST00000648758.1 | c.865_867del | p.Leu289del | inframe_deletion | 8/9 | P1 | |||
ALDOB | ENST00000649902.1 | c.865_867del | p.Leu289del | inframe_deletion | 7/7 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary fructosuria Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 10, 1990 | - - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at