8-106679270-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001198533.2(OXR1):c.281C>G(p.Pro94Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000163 in 1,598,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
OXR1
NM_001198533.2 missense
NM_001198533.2 missense
Scores
9
5
3
Clinical Significance
Conservation
PhyloP100: 5.82
Genes affected
OXR1 (HGNC:15822): (oxidation resistance 1) Predicted to enable oxidoreductase activity. Predicted to be involved in response to oxidative stress. Predicted to act upstream of or within several processes, including adult walking behavior; negative regulation of neuron death; and negative regulation of peptidyl-cysteine S-nitrosylation. Predicted to be located in mitochondrion and nucleolus. Predicted to be active in nucleus. Implicated in cerebellar hyplasia/atrophy, epilepsy, and global developmental delay. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.773
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OXR1 | NM_001198533.2 | c.281C>G | p.Pro94Arg | missense_variant | 4/17 | ENST00000517566.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OXR1 | ENST00000517566.7 | c.281C>G | p.Pro94Arg | missense_variant | 4/17 | 1 | NM_001198533.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151992Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249878Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135172
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GnomAD4 exome AF: 0.0000166 AC: 24AN: 1446038Hom.: 0 Cov.: 26 AF XY: 0.0000153 AC XY: 11AN XY: 720404
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151992Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74232
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | The c.284C>G (p.P95R) alteration is located in exon 3 (coding exon 3) of the OXR1 gene. This alteration results from a C to G substitution at nucleotide position 284, causing the proline (P) at amino acid position 95 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
D;.;D;.;D;D
Vest4
MutPred
0.56
.;.;Gain of MoRF binding (P = 0.0082);.;.;.;
MVP
MPC
0.52
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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