rs786204830
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5
The NM_001098.3(ACO2):c.2328_2331del(p.Lys776AsnfsTer49) variant causes a frameshift change involving the alteration of a conserved nucleotide. 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: 32)
Consequence
ACO2
NM_001098.3 frameshift
NM_001098.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.05
Genes affected
ACO2 (HGNC:118): (aconitase 2) The protein encoded by this gene belongs to the aconitase/IPM isomerase family. It is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. This protein is encoded in the nucleus and functions in the mitochondrion. It was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15(PRSS15), also known as Lon protease, after oxidative modification. [provided by RefSeq, Jul 2008]
POLR3H (HGNC:30349): (RNA polymerase III subunit H) Enables DNA-directed 5'-3' RNA polymerase activity. Involved in transcription by RNA polymerase III. Located in centrosome and nucleoplasm. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 851 codons.
PP5
?
Variant 22-41528594-TGAAG-T is Pathogenic according to our data. Variant chr22-41528594-TGAAG-T is described in ClinVar as [Pathogenic]. Clinvar id is 189314.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-41528594-TGAAG-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACO2 | NM_001098.3 | c.2328_2331del | p.Lys776AsnfsTer49 | frameshift_variant | 18/18 | ENST00000216254.9 | |
POLR3H | NM_001018050.4 | c.*685_*688del | 3_prime_UTR_variant | 6/6 | ENST00000355209.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACO2 | ENST00000216254.9 | c.2328_2331del | p.Lys776AsnfsTer49 | frameshift_variant | 18/18 | 1 | NM_001098.3 | P3 | |
POLR3H | ENST00000355209.9 | c.*685_*688del | 3_prime_UTR_variant | 6/6 | 1 | NM_001018050.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Infantile cerebellar-retinal degeneration Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at