10-97601957-ACTG-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5

The NM_138413.4(HOGA1):​c.803_805delTGC​(p.Leu268del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HOGA1
NM_138413.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.63
Variant links:
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_138413.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 10-97601957-ACTG-A is Pathogenic according to our data. Variant chr10-97601957-ACTG-A is described in ClinVar as [Pathogenic]. Clinvar id is 204288.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HOGA1NM_138413.4 linkuse as main transcriptc.803_805delTGC p.Leu268del disruptive_inframe_deletion 6/7 ENST00000370646.9 NP_612422.2 Q86XE5-1
HOGA1NM_001134670.2 linkuse as main transcriptc.314_316delTGC p.Leu105del disruptive_inframe_deletion 2/3 NP_001128142.1 Q86XE5-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HOGA1ENST00000370646.9 linkuse as main transcriptc.803_805delTGC p.Leu268del disruptive_inframe_deletion 6/71 NM_138413.4 ENSP00000359680.4 Q86XE5-1
ENSG00000249967ENST00000370649.3 linkuse as main transcriptc.314_316delTGC p.Leu105del disruptive_inframe_deletion 2/102 ENSP00000359683.3 E9PAM4
HOGA1ENST00000370647.8 linkuse as main transcriptc.314_316delTGC p.Leu105del disruptive_inframe_deletion 2/31 ENSP00000359681.4 Q86XE5-3
HOGA1ENST00000370642.4 linkuse as main transcriptc.212_214delTGC p.Leu71del disruptive_inframe_deletion 3/45 ENSP00000359676.4 H7BY76

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460710
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
726578
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Primary hyperoxaluria type 3 Pathogenic:1
Pathogenic, no assertion criteria providedresearchClinical Biochemistry Laboratory, Health Services LaboratoryNov 27, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs796052092; hg19: chr10-99361714; API