8-106519050-C-A

Variant names:

• chr8-106519050-C-A
• rs201198313
• NM_001198533.2:c.131C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001198533.2(OXR1):​c.131C>A​(p.Thr44Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,551,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: OXR1 NM_001198533.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29
• Publications: 3 publications found

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-AS1 (HGNC:55533): (OXR1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06300315).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198533.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXR1	NM_001198533.2	MANE Select	c.131C>A	p.Thr44Asn	missense	Exon 3 of 17	NP_001185462.1	Q8N573-8
	OXR1	NM_001198532.1		c.134C>A	p.Thr45Asn	missense	Exon 2 of 16	NP_001185461.1	Q8N573-1
	OXR1	NM_018002.3		c.131C>A	p.Thr44Asn	missense	Exon 3 of 16	NP_060472.2	Q8N573-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXR1	ENST00000517566.7	TSL:1 MANE Select	c.131C>A	p.Thr44Asn	missense	Exon 3 of 17	ENSP00000429205.2	Q8N573-8
	OXR1	ENST00000442977.6	TSL:2	c.134C>A	p.Thr45Asn	missense	Exon 2 of 16	ENSP00000405424.2	Q8N573-1
	OXR1	ENST00000531443.6	TSL:5	c.131C>A	p.Thr44Asn	missense	Exon 3 of 16	ENSP00000431966.1	Q8N573-5

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000456

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000139 AC: 22 AN: 158576 AF XY: 0.000156

Gnomad AFR exome AF: 0.000120

Gnomad AMR exome AF: 0.0000808

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000261 AC: 366 AN: 1399710 Hom.: 0 Cov.: 30 AF XY: 0.000274 AC XY: 189 AN XY: 690360

African (AFR) AF: 0.0000633 AC: 2 AN: 31594

American (AMR) AF: 0.0000560 AC: 2 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35740

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.000325 AC: 351 AN: 1078892

Other (OTH) AF: 0.000172 AC: 10 AN: 58148

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152080 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74282

African (AFR) AF: 0.0000483 AC: 2 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000359 Hom.: 0

Bravo AF: 0.000151

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000943 AC: 3

ExAC AF: 0.000191 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.091
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.43	T
Polyphen		0.95	P
Vest4		0.24
MVP		0.30
MPC		0.17
ClinPred		0.039	T
GERP RS		3.3
Varity_R		0.10
gMVP		0.37
Mutation Taster		=93/7	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs201198313; hg19: chr8-107531278;