rs745492359
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001303.4(COX10):c.1061G>A(p.Arg354Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000614 in 1,613,534 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R354W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001303.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COX10 | NM_001303.4 | c.1061G>A | p.Arg354Gln | missense_variant | 7/7 | ENST00000261643.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COX10 | ENST00000261643.8 | c.1061G>A | p.Arg354Gln | missense_variant | 7/7 | 1 | NM_001303.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000362 AC: 9AN: 248476Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134520
GnomAD4 exome AF: 0.0000630 AC: 92AN: 1461346Hom.: 0 Cov.: 32 AF XY: 0.0000702 AC XY: 51AN XY: 726964
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74342
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 354 of the COX10 protein (p.Arg354Gln). This variant is present in population databases (rs745492359, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with COX10-related conditions. ClinVar contains an entry for this variant (Variation ID: 444401). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COX10 protein function with a negative predictive value of 80%. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2022 | The c.1061G>A (p.R354Q) alteration is located in exon 7 (coding exon 7) of the COX10 gene. This alteration results from a G to A substitution at nucleotide position 1061, causing the arginine (R) at amino acid position 354 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Mitochondrial complex 4 deficiency, nuclear type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics | Jan 31, 2023 | - - |
Leigh syndrome;C5435656:Mitochondrial complex IV deficiency, nuclear type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at