rs149671008
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_000035.4(ALDOB):āc.156T>Gā(p.Thr52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000577 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0028 ( 0 hom., cov: 32)
Exomes š: 0.00035 ( 0 hom. )
Consequence
ALDOB
NM_000035.4 synonymous
NM_000035.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -10.6
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 Benign. Variant got -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
?
Variant 9-101429923-A-C is Benign according to our data. Variant chr9-101429923-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 254731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-101429923-A-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-10.6 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00277 (421/152196) while in subpopulation AFR AF= 0.00922 (383/41536). AF 95% confidence interval is 0.00846. There are 0 homozygotes in gnomad4. There are 190 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDOB | NM_000035.4 | c.156T>G | p.Thr52= | synonymous_variant | 3/9 | ENST00000647789.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDOB | ENST00000647789.2 | c.156T>G | p.Thr52= | synonymous_variant | 3/9 | NM_000035.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00276 AC: 420AN: 152078Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000712 AC: 179AN: 251304Hom.: 0 AF XY: 0.000464 AC XY: 63AN XY: 135814
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GnomAD4 exome AF: 0.000350 AC: 511AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.000276 AC XY: 201AN XY: 727248
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GnomAD4 genome ? AF: 0.00277 AC: 421AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.00255 AC XY: 190AN XY: 74396
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary fructosuria Benign:3
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 07, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 10, 2019 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 01, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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