8-106692712-TAAA-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001198533.2(OXR1):c.526-4_526-2del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,165,484 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000072 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: OXR1 NM_001198533.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.226

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-106692712-TAAA-T is Benign according to our data. Variant chr8-106692712-TAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 3044824.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXR1	NM_001198533.2	c.526-4_526-2del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000517566.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXR1	ENST00000517566.7	c.526-4_526-2del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001198533.2	P3

Frequencies

GnomAD3 genomes AF: 0.00000717 AC: 1 AN: 139488 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

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: 0.0000156

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000425 AC: 32 AN: 75268 Hom.: 0 AF XY: 0.000480 AC XY: 20 AN XY: 41684

Gnomad AFR exome AF: 0.000541

Gnomad AMR exome AF: 0.000321

Gnomad ASJ exome AF: 0.000785

Gnomad EAS exome AF: 0.000612

Gnomad SAS exome AF: 0.000609

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.000357

Gnomad OTH exome AF: 0.00139

GnomAD4 exome AF: 0.000230 AC: 236 AN: 1025996 Hom.: 0 AF XY: 0.000222 AC XY: 112 AN XY: 503446

Gnomad4 AFR exome AF: 0.000223

Gnomad4 AMR exome AF: 0.000372

Gnomad4 ASJ exome AF: 0.000302

Gnomad4 EAS exome AF: 0.000267

Gnomad4 SAS exome AF: 0.000250

Gnomad4 FIN exome AF: 0.000138

Gnomad4 NFE exome AF: 0.000224

Gnomad4 OTH exome AF: 0.000263

GnomAD4 genome AF: 0.00000717 AC: 1 AN: 139488 Hom.: 0 Cov.: 30 AF XY: 0.0000148 AC XY: 1 AN XY: 67564

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000156

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

OXR1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs750764834; hg19: chr8-107704940;