Variant 8-106706393-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001198533.2(OXR1):c.872A>T(p.Gln291Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000446 in 1,568,702 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

OXR1
NM_001198533.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

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]

OXR1 links:

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=0.10977009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXR1	NM_001198533.2 link	c.872A>T	p.Gln291Leu	missense_variant	9/17	ENST00000517566.7	NP_001185462.1	Q8N573-8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXR1	ENST00000517566.7 link	c.872A>T	p.Gln291Leu	missense_variant	9/17	1	NM_001198533.2	ENSP00000429205.2		Q8N573-8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.00000470

AC:

AN:

212910

Hom.:

AF XY:

0.00

AC XY:

AN XY:

116236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000199

GnomAD4 exome

AF:

0.00000353

AC:

AN:

1416538

Hom.:

Cov.:

AF XY:

0.00000426

AC XY:

AN XY:

704204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000979

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000342

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

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

Sep 05, 2024

The c.875A>T (p.Q292L) alteration is located in exon 8 (coding exon 8) of the OXR1 gene. This alteration results from a A to T substitution at nucleotide position 875, causing the glutamine (Q) at amino acid position 292 to be replaced by a leucine (L). 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

0.072

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.048

.;.;T;.;.

Eigen

Benign

0.043

Eigen_PC

Benign

0.076

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

T;T;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.0

.;.;L;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.0

N;N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.14

T;T;T;T;T

Sift4G

Benign

0.24

T;T;T;T;T

Polyphen

0.0

B;.;B;B;B

Vest4

0.16

MutPred

0.31

.;.;Loss of loop (P = 0.0112);.;.;

MVP

0.41

MPC

0.094

ClinPred

0.090

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over