rs1057518833
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_001098.3(ACO2):c.75C>T(p.Val25Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,498 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
ACO2
NM_001098.3 synonymous
NM_001098.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.94
Publications
1 publications found
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]
ACO2 Gene-Disease associations (from GenCC):
- infantile cerebellar-retinal degenerationInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
- optic atrophy 9Inheritance: Unknown, AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
- autosomal recessive optic atrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP7
Synonymous conserved (PhyloP=1.94 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001098.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ACO2 | NM_001098.3 | MANE Select | c.75C>T | p.Val25Val | synonymous | Exon 2 of 18 | NP_001089.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ACO2 | ENST00000216254.9 | TSL:1 MANE Select | c.75C>T | p.Val25Val | synonymous | Exon 2 of 18 | ENSP00000216254.4 | ||
| ACO2 | ENST00000878390.1 | c.75C>T | p.Val25Val | synonymous | Exon 2 of 20 | ENSP00000548449.1 | |||
| ACO2 | ENST00000878384.1 | c.75C>T | p.Val25Val | synonymous | Exon 2 of 19 | ENSP00000548443.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461498Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727058 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461498
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727058
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86244
European-Finnish (FIN)
AF:
AC:
0
AN:
53186
Middle Eastern (MID)
AF:
AC:
0
AN:
5660
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1112004
Other (OTH)
AF:
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Neurodegeneration;C0557874:Global developmental delay;C1850456:Progressive microcephaly;C3805839:Central hypoventilation;C4551584:Brain atrophy (1)
-
1
-
Optic atrophy 9 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
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