Genetic Variant ATXN8OS:n.576C>T (chr13-70130745-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000424524.2(ATXN8OS):n.576C>T 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 0.0000552 in 398,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

ATXN8OS
ENST00000424524.2 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.668

Variant links:

Genes affected

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]

ATXN8OS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 13-70130745-C-T is Benign according to our data. Variant chr13-70130745-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3036741.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.648C>T	non_coding_transcript_exon_variant	Exon 4 of 5
ATXN8OS	NR_185836.1 link	n.989C>T	non_coding_transcript_exon_variant	Exon 4 of 7
ATXN8OS	NR_185838.1 link	n.521C>T	non_coding_transcript_exon_variant	Exon 4 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ATXN8OS	ENST00000424524.2 link	n.576C>T	non_coding_transcript_exon_variant	Exon 4 of 4	1
ATXN8OS	ENST00000414504.6 link	n.856C>T	non_coding_transcript_exon_variant	Exon 4 of 5	5
ATXN8OS	ENST00000665905.1 link	n.740C>T	non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000569

AC:

AN:

246236

Hom.:

Cov.:

AF XY:

0.0000641

AC XY:

AN XY:

124764

show subpopulations

Gnomad4 AFR exome

AF:

0.000139

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.000108

Gnomad4 EAS exome

AF:

0.0000874

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000380

Gnomad4 OTH exome

AF:

0.000122

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATXN8OS-related disorder

Benign:1

Apr 04, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.5

DANN

Benign

0.65

Splicing

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