16-85805022-G-A
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001861.6(COX4I1):c.159G>A(p.Lys53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 1,614,072 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00056 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00040 ( 6 hom. )
Consequence
COX4I1
NM_001861.6 synonymous
NM_001861.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.53
Genes affected
COX4I1 (HGNC:2265): (cytochrome c oxidase subunit 4I1) Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane. The complex consists of 13 mitochondrial- and nuclear-encoded subunits. The mitochondrially-encoded subunits perform the electron transfer and proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex. This gene encodes the nuclear-encoded subunit IV isoform 1 of the human mitochondrial respiratory chain enzyme. It is located at the 3' of the NOC4 (neighbor of COX4) gene in a head-to-head orientation, and shares a promoter with it. Pseudogenes related to this gene are located on chromosomes 13 and 14. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 16-85805022-G-A is Benign according to our data. Variant chr16-85805022-G-A is described in ClinVar as [Benign]. Clinvar id is 710577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=3.53 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COX4I1 | NM_001861.6 | c.159G>A | p.Lys53= | synonymous_variant | 3/5 | ENST00000253452.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COX4I1 | ENST00000253452.8 | c.159G>A | p.Lys53= | synonymous_variant | 3/5 | 1 | NM_001861.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000565 AC: 86AN: 152228Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00205 AC: 515AN: 251096Hom.: 7 AF XY: 0.00147 AC XY: 200AN XY: 135848
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GnomAD4 exome AF: 0.000400 AC: 585AN: 1461844Hom.: 6 Cov.: 42 AF XY: 0.000330 AC XY: 240AN XY: 727212
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GnomAD4 genome ? AF: 0.000565 AC: 86AN: 152228Hom.: 0 Cov.: 34 AF XY: 0.000712 AC XY: 53AN XY: 74388
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 22, 2018 | - - |
COX4I1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 11, 2023 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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