chr8-106692777-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001198533.2(OXR1):​c.575G>A​(p.Gly192Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,595,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

OXR1
NM_001198533.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10921264).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OXR1NM_001198533.2 linkuse as main transcriptc.575G>A p.Gly192Asp missense_variant 7/17 ENST00000517566.7 NP_001185462.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OXR1ENST00000517566.7 linkuse as main transcriptc.575G>A p.Gly192Asp missense_variant 7/171 NM_001198533.2 ENSP00000429205 P3Q8N573-8

Frequencies

GnomAD3 genomes
AF:
0.0000266
AC:
4
AN:
150486
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000199
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000324
AC:
8
AN:
247150
Hom.:
0
AF XY:
0.0000224
AC XY:
3
AN XY:
133800
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000180
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000111
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000831
AC:
12
AN:
1444708
Hom.:
0
Cov.:
28
AF XY:
0.00000834
AC XY:
6
AN XY:
719308
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000253
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000255
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000266
AC:
4
AN:
150558
Hom.:
0
Cov.:
31
AF XY:
0.0000136
AC XY:
1
AN XY:
73364
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000199
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsJun 10, 2022The c.578G>A (p.G193D) alteration is located in exon 6 (coding exon 6) of the OXR1 gene. This alteration results from a G to A substitution at nucleotide position 578, causing the glycine (G) at amino acid position 193 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Benign
0.89
DEOGEN2
Benign
0.024
.;.;T;.;.
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.72
T;T;T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.11
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
.;.;L;.;.
MutationTaster
Benign
0.80
D;D;N;N;N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.86
N;N;N;N;N
REVEL
Benign
0.052
Sift
Benign
0.19
T;T;T;T;T
Sift4G
Benign
0.31
T;T;T;T;T
Polyphen
0.0010
B;.;B;B;B
Vest4
0.41
MutPred
0.19
.;.;Gain of solvent accessibility (P = 0.0638);.;.;
MVP
0.48
MPC
0.13
ClinPred
0.056
T
GERP RS
3.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.040
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs540340584; hg19: chr8-107705005; API