rs875989827
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_001206641.3(COA6):c.286T>C(p.Trp96Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
COA6
NM_001206641.3 missense
NM_001206641.3 missense
Scores
8
8
1
Clinical Significance
Conservation
PhyloP100: 5.20
Genes affected
COA6 (HGNC:18025): (cytochrome c oxidase assembly factor 6) This gene encodes a member of the cytochrome c oxidase subunit 6B family. The encoded protein associates with cytochrome c oxidase may act has an cytochrome c oxidase mitochondrial respiratory complex VI assembly factor. Mutations in this gene may be associated with fatal infantile cardiomyopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.962
PP5
?
Variant 1-234374303-T-C is Pathogenic according to our data. Variant chr1-234374303-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 204622.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-234374303-T-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COA6 | NM_001206641.3 | c.286T>C | p.Trp96Arg | missense_variant | 2/3 | ENST00000366615.10 | |
COA6 | NM_001012985.2 | c.196T>C | p.Trp66Arg | missense_variant | 2/3 | ||
COA6 | NM_001301733.1 | c.58T>C | p.Trp20Arg | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COA6 | ENST00000366615.10 | c.286T>C | p.Trp96Arg | missense_variant | 2/3 | 1 | NM_001206641.3 | ||
COA6 | ENST00000366613.1 | c.196T>C | p.Trp66Arg | missense_variant | 2/3 | 1 | |||
COA6 | ENST00000366612.1 | c.58T>C | p.Trp20Arg | missense_variant | 1/2 | 1 | P1 | ||
COA6 | ENST00000619305.1 | c.58T>C | p.Trp20Arg | missense_variant | 2/3 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
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
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;D
REVEL
Pathogenic
Sift
Uncertain
D;.;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;.;D;.
Vest4
MutPred
0.76
.;.;Gain of disorder (P = 0.0047);.;
MVP
MPC
1.8
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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