13-70139377-ACTACTACTGCTGCTGCTG-A

Position:

• chr13-70139377-ACTACTACTGCTGCTGCTG-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NR_002717.2(ATXN8OS):​n.1099_1116del variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 645,424 control chromosomes in the GnomAD database, including 415 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.056 (379 hom., cov: 0)
  • Exomes 𝑓: 0.0027 (36 hom.)
• Consequence: ATXN8OS NR_002717.2 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.50

Genes affected

(HGNC:):

ATXN8OS (HGNC:10561): (ATXN8 opposite strand lncRNA) This gene is an antisense transcript to the KLHL1 gene (homolog to the Drosophila KELCH gene); it does not itself appear to be protein coding. A TAC/TGC trinucleotide repeat expansion that is incorporated into this gene transcript, but not the KLHL1 transcript, causes spinocerebellar ataxia type 8. Presumably the expansion interferes with normal antisense function of this transcript. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 13-70139377-ACTACTACTGCTGCTGCTG-A is Benign according to our data. Variant chr13-70139377-ACTACTACTGCTGCTGCTG-A is described in ClinVar as [Benign]. Clinvar id is 3039106.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN8OS	NR_002717.2	n.1099_1116del		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000673087.1	n.37_54del		non_coding_transcript_exon_variant	1/1
ATXN8OS	ENST00000678624.1	n.500-7975_500-7958del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 5505 AN: 98162 Hom.: 379 Cov.: 0

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.00176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00164

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0217

Gnomad NFE AF: 0.000997

Gnomad OTH AF: 0.0385

GnomAD4 exome AF: 0.00275 AC: 1504 AN: 547206 Hom.: 36 AF XY: 0.00231 AC XY: 673 AN XY: 291336

Gnomad4 AFR exome AF: 0.0763

Gnomad4 AMR exome AF: 0.00348

Gnomad4 ASJ exome AF: 0.0000554

Gnomad4 EAS exome AF: 0.0000335

Gnomad4 SAS exome AF: 0.0000203

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000396

Gnomad4 OTH exome AF: 0.00669

GnomAD4 genome AF: 0.0561 AC: 5510 AN: 98218 Hom.: 379 Cov.: 0 AF XY: 0.0557 AC XY: 2640 AN XY: 47380

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.00176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00109

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000997

Gnomad4 OTH AF: 0.0385

Alfa AF: 0.0325 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ATXN8OS-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 26, 2023

This variant is classified as 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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1186729821; hg19: chr13-70713509;