chr12-50120164-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032901.4(COX14):c.121C>T(p.Arg41Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000979 in 1,614,152 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. R41H) has been classified as Uncertain significance.
Frequency
Consequence
NM_032901.4 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 |
---|---|---|---|---|---|---|---|
COX14 | NM_032901.4 | c.121C>T | p.Arg41Cys | missense_variant | 2/2 | ENST00000550487.6 | |
COX14 | NM_001257133.2 | c.121C>T | p.Arg41Cys | missense_variant | 3/3 | ||
COX14 | NM_001257134.2 | c.121C>T | p.Arg41Cys | missense_variant | 2/2 | ||
COX14 | XM_047429769.1 | c.121C>T | p.Arg41Cys | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COX14 | ENST00000550487.6 | c.121C>T | p.Arg41Cys | missense_variant | 2/2 | 1 | NM_032901.4 | P1 | |
ENST00000548468.2 | n.105+7863C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152172Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000211 AC: 53AN: 251424Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135886
GnomAD4 exome AF: 0.0000923 AC: 135AN: 1461862Hom.: 0 Cov.: 31 AF XY: 0.0000976 AC XY: 71AN XY: 727228
GnomAD4 genome AF: 0.000151 AC: 23AN: 152290Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74448
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 21, 2018 | p.Arg41Cys (CGC>TGC): c.121 C>T in exon 2 of the COX14 gene (NM_032901.3). The R41C missense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is non-conservative in that a positively charged Arginine residue is replaced by an uncharged Cysteine residue and the introduction of a Cysteine residue could affect disulfide bonds in the COX14 protein. This change occurs at a conserved position in the COX14 protein. In-silico analyses are not consistent in their predictions of whether or not R41C is damaging to the COX14 protein. Therefore, based on the currently available information, it is unclear whether R41C is a disease-causing mutation or a rare benign variant. The variant is found in LAPDH-MITOP,MITONUC-MITOP panel(s). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 41 of the COX14 protein (p.Arg41Cys). This variant is present in population databases (rs148220171, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with COX14-related conditions. ClinVar contains an entry for this variant (Variation ID: 214249). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.121C>T (p.R41C) alteration is located in exon 2 (coding exon 1) of the COX14 gene. This alteration results from a C to T substitution at nucleotide position 121, causing the arginine (R) at amino acid position 41 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at