rs751944867
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_205767.3(MICOS13):c.150delC(p.Ala51ProfsTer39) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
MICOS13
NM_205767.3 frameshift
NM_205767.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -6.75
Publications
3 publications found
Genes affected
MICOS13 (HGNC:33702): (mitochondrial contact site and cristae organizing system subunit 13) Involved in cristae formation. Located in mitochondrial crista junction and nucleoplasm. Part of MICOS complex. Implicated in combined oxidative phosphorylation deficiency 37. [provided by Alliance of Genome Resources, Apr 2022]
RPL36 (HGNC:13631): (ribosomal protein L36) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L36E family of ribosomal proteins. It is located in the cytoplasm. Transcript variants derived from alternative splicing exist; they encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-5679642-CG-C is Pathogenic according to our data. Variant chr19-5679642-CG-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1526386.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_205767.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| MICOS13 | MANE Select | c.150delC | p.Ala51ProfsTer39 | frameshift | Exon 2 of 4 | NP_991330.1 | Q5XKP0 | ||
| MICOS13 | c.216delC | p.Ala73ProfsTer39 | frameshift | Exon 3 of 5 | NP_001295169.1 | A0A140TA86 | |||
| MICOS13 | c.216delC | p.Ala73ProfsTer39 | frameshift | Exon 2 of 4 | NP_001352690.1 | A0A140TA86 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MICOS13 | TSL:1 MANE Select | c.150delC | p.Ala51ProfsTer39 | frameshift | Exon 2 of 4 | ENSP00000309561.3 | Q5XKP0 | ||
| MICOS13 | TSL:2 | c.216delC | p.Ala73ProfsTer39 | frameshift | Exon 2 of 4 | ENSP00000468723.1 | A0A140TA86 | ||
| MICOS13 | c.150delC | p.Ala51ProfsTer48 | frameshift | Exon 2 of 4 | ENSP00000566410.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.0000163 AC: 4AN: 245816 AF XY: 0.0000150 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
245816
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1458530Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 725620 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
4
AN:
1458530
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
725620
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
2
AN:
33364
American (AMR)
AF:
AC:
1
AN:
44006
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25972
East Asian (EAS)
AF:
AC:
0
AN:
39674
South Asian (SAS)
AF:
AC:
0
AN:
86092
European-Finnish (FIN)
AF:
AC:
0
AN:
52220
Middle Eastern (MID)
AF:
AC:
0
AN:
5694
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111224
Other (OTH)
AF:
AC:
0
AN:
60284
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000123629), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.313
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
1
-
Combined oxidative phosphorylation deficiency 37 (1)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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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