8-106692810-C-T

Variant names:

• chr8-106692810-C-T
• rs1829446642
• NM_001198533.2:c.608C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001198533.2(OXR1):​c.608C>T​(p.Ser203Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: OXR1 NM_001198533.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 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 Gene-Disease associations (from GenCC):

• isolated cerebellar hypoplasia/agenesis

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.608C>T	p.Ser203Phe	missense	Exon 7 of 17	NP_001185462.1	Q8N573-8
	OXR1	NM_001198532.1		c.611C>T	p.Ser204Phe	missense	Exon 6 of 16	NP_001185461.1	Q8N573-1
	OXR1	NM_018002.3		c.608C>T	p.Ser203Phe	missense	Exon 7 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.608C>T	p.Ser203Phe	missense	Exon 7 of 17	ENSP00000429205.2	Q8N573-8
	OXR1	ENST00000312046.10	TSL:1	c.587C>T	p.Ser196Phe	missense	Exon 5 of 14	ENSP00000311026.6	Q8N573-2
	OXR1	ENST00000438229.6	TSL:1	n.*364C>T		non_coding_transcript_exon	Exon 5 of 7	ENSP00000414992.2	E5RFD1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.27		Loss of phosphorylation at S204 (P = 0.017)
MVP		0.52
MPC		0.53
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.76
gMVP		0.67
Mutation Taster		=216/84	polymorphism

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

Other links and lift over

dbSNP: rs1829446642; hg19: chr8-107705038; COSMIC: COSV56333352; COSMIC: COSV56333352;