rs11817730
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_138413.4(HOGA1):c.212-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,613,546 control chromosomes in the GnomAD database, including 31,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.20 ( 3050 hom., cov: 32)
Exomes 𝑓: 0.19 ( 28312 hom. )
Consequence
HOGA1
NM_138413.4 intron
NM_138413.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.86
Genes affected
HOGA1 (HGNC:25155): (4-hydroxy-2-oxoglutarate aldolase 1) The authors of PMID:20797690 cloned this gene while searching for genes in a region of chromosome 10 linked to primary hyperoxalurea type III. They noted that even though the encoded protein has been described as a mitochondrial dihydrodipicolinate synthase-like enzyme, it shares little homology with E. coli dihydrodipicolinate synthase (Dhdps), particularly in the putative substrate-binding region. Moreover, neither lysine biosynthesis nor sialic acid metabolism, for which Dhdps is responsible, occurs in vertebrate mitochondria. They propose that this gene encodes mitochondrial 4-hydroxyl-2-oxoglutarate aldolase (EC 4.1.3.16), which catalyzes the final step in the metabolic pathway of hydroxyproline, releasing glyoxylate and pyruvate. This gene is predominantly expressed in the liver and kidney, and mutations in this gene are found in patients with primary hyperoxalurea type III. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
?
Variant 10-97598754-A-G is Benign according to our data. Variant chr10-97598754-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 204254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOGA1 | NM_138413.4 | c.212-21A>G | intron_variant | ENST00000370646.9 | |||
HOGA1 | NM_001134670.2 | c.212-3103A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOGA1 | ENST00000370646.9 | c.212-21A>G | intron_variant | 1 | NM_138413.4 | P1 | |||
HOGA1 | ENST00000370647.8 | c.212-3103A>G | intron_variant | 1 | |||||
HOGA1 | ENST00000465608.1 | n.593-21A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.196 AC: 29882AN: 152074Hom.: 3045 Cov.: 32
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GnomAD3 exomes AF: 0.185 AC: 46483AN: 251460Hom.: 4437 AF XY: 0.184 AC XY: 25015AN XY: 135906
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GnomAD4 exome AF: 0.195 AC: 284464AN: 1461354Hom.: 28312 Cov.: 34 AF XY: 0.194 AC XY: 141039AN XY: 726992
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GnomAD4 genome ? AF: 0.197 AC: 29917AN: 152192Hom.: 3050 Cov.: 32 AF XY: 0.195 AC XY: 14542AN XY: 74406
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary hyperoxaluria type 3 Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | research | Clinical Biochemistry Laboratory, Health Services Laboratory | Nov 27, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
La Branchor
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