12-50120177-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_032901.4(COX14):c.134G>A(p.Arg45His) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,872 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: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
COX14
NM_032901.4 missense
NM_032901.4 missense
Scores
8
9
Clinical Significance
Conservation
PhyloP100: 4.41
Genes affected
COX14 (HGNC:28216): (cytochrome c oxidase assembly factor COX14) This gene encodes a small single-pass transmembrane protein that localizes to mitochondria. This protein may play a role in coordinating the early steps of cytochrome c oxidase (COX; also known as complex IV) subunit assembly and, in particular, the synthesis and assembly of the COX I subunit of the holoenzyme. Mutations in this gene have been associated with mitochondrial complex IV deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4047047).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COX14 | NM_032901.4 | c.134G>A | p.Arg45His | missense_variant | 2/2 | ENST00000550487.6 | |
COX14 | NM_001257133.2 | c.134G>A | p.Arg45His | missense_variant | 3/3 | ||
COX14 | NM_001257134.2 | c.134G>A | p.Arg45His | missense_variant | 2/2 | ||
COX14 | XM_047429769.1 | c.134G>A | p.Arg45His | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COX14 | ENST00000550487.6 | c.134G>A | p.Arg45His | missense_variant | 2/2 | 1 | NM_032901.4 | P1 | |
ENST00000548468.2 | n.105+7876G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251348Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135862
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727240
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GnomAD4 genome Cov.: 33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2022 | This variant is present in population databases (rs752679893, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 45 of the COX14 protein (p.Arg45His). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with COX14-related conditions. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
D;D;D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0078);Loss of MoRF binding (P = 0.0078);Loss of MoRF binding (P = 0.0078);Loss of MoRF binding (P = 0.0078);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at