chr22-50523612-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PM4PP5
The NM_005138.3(SCO2):c.800G>C(p.Ter267Serext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,202 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Consequence
SCO2
NM_005138.3 stop_lost
NM_005138.3 stop_lost
Scores
6
Clinical Significance
Conservation
PhyloP100: -0.174
Publications
0 publications found
Genes affected
SCO2 (HGNC:10604): (synthesis of cytochrome C oxidase 2) Cytochrome c oxidase (COX) catalyzes the transfer of electrons from cytochrome c to molecular oxygen, which helps to maintain the proton gradient across the inner mitochondrial membrane that is necessary for aerobic ATP production. Human COX is a multimeric protein complex that requires several assembly factors; this gene encodes one of the COX assembly factors. The encoded protein is a metallochaperone that is involved in the biogenesis of cytochrome c oxidase subunit II. Mutations in this gene are associated with fatal infantile encephalocardiomyopathy and myopia 6. [provided by RefSeq, Oct 2014]
NCAPH2 (HGNC:25071): (non-SMC condensin II complex subunit H2) This gene encodes one of the non-SMC subunits of the condensin II complex. This complex plays an essential role in mitotic chromosome assembly. Alternate splicing of this gene results in multiple transcript variants.[provided by RefSeq, May 2010]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_005138.3 Downstream stopcodon found after 6 codons.
PP5
Variant 22-50523612-C-G is Pathogenic according to our data. Variant chr22-50523612-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1806547.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005138.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| SCO2 | NM_005138.3 | MANE Select | c.800G>C | p.Ter267Serext*? | stop_lost | Exon 2 of 2 | NP_005129.2 | O43819 | |
| NCAPH2 | NM_152299.4 | MANE Select | c.*237C>G | 3_prime_UTR | Exon 20 of 20 | NP_689512.2 | Q6IBW4-1 | ||
| SCO2 | NM_001169109.2 | c.800G>C | p.Ter267Serext*? | stop_lost | Exon 2 of 2 | NP_001162580.1 | O43819 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SCO2 | ENST00000395693.8 | TSL:1 MANE Select | c.800G>C | p.Ter267Serext*? | stop_lost | Exon 2 of 2 | ENSP00000379046.4 | O43819 | |
| NCAPH2 | ENST00000420993.7 | TSL:1 MANE Select | c.*237C>G | 3_prime_UTR | Exon 20 of 20 | ENSP00000410088.2 | Q6IBW4-1 | ||
| SCO2 | ENST00000252785.3 | TSL:2 | c.800G>C | p.Ter267Serext*? | stop_lost | Exon 2 of 2 | ENSP00000252785.3 | O43819 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152202
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
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Gnomad AMR
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Gnomad ASJ
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Gnomad SAS
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Gnomad OTH
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GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74356 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152202
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
74356
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41450
American (AMR)
AF:
AC:
1
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68046
Other (OTH)
AF:
AC:
1
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
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Allele balance
Age Distribution
Genome Het
Variant carriers
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Alfa
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ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
1
-
-
Myopia 6;C5399977:Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (1)
-
1
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
PhyloP100
Vest4
GERP RS
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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