NM_005138.3:c.762G>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_005138.3(SCO2):c.762G>A(p.Val254Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,612 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 Likely benign (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SCO2
NM_005138.3 synonymous
NM_005138.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.245
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]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 22-50523650-C-T is Benign according to our data. Variant chr22-50523650-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 764239.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.245 with no splicing effect.
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.762G>A | p.Val254Val | synonymous | Exon 2 of 2 | NP_005129.2 | O43819 | |
| NCAPH2 | NM_152299.4 | MANE Select | c.*275C>T | 3_prime_UTR | Exon 20 of 20 | NP_689512.2 | Q6IBW4-1 | ||
| SCO2 | NM_001169109.2 | c.762G>A | p.Val254Val | synonymous | 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.762G>A | p.Val254Val | synonymous | Exon 2 of 2 | ENSP00000379046.4 | O43819 | |
| NCAPH2 | ENST00000420993.7 | TSL:1 MANE Select | c.*275C>T | 3_prime_UTR | Exon 20 of 20 | ENSP00000410088.2 | Q6IBW4-1 | ||
| SCO2 | ENST00000252785.3 | TSL:2 | c.762G>A | p.Val254Val | synonymous | Exon 2 of 2 | ENSP00000252785.3 | O43819 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD2 exomes AF: 0.0000119 AC: 3AN: 251282 AF XY: 0.0000221 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
251282
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461612Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727112 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461612
Hom.:
Cov.:
35
AF XY:
AC XY:
1
AN XY:
727112
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53210
Middle Eastern (MID)
AF:
AC:
0
AN:
5730
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1112002
Other (OTH)
AF:
AC:
0
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
34
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not provided (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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