Genetic Variant ATXN8OS:n.1134_1148delTGCTGCTGCTGCTGC (chr13-70139383-ACTGCTGCTGCTGCTG-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000414504.6(ATXN8OS):n.1134_1148delTGCTGCTGCTGCTGC variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 458,196 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

ATXN8OS
ENST00000414504.6 splice_region, non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.190

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 8
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ATXN8OS links:

ENSG00000288330 (HGNC:32925):

ENSG00000288330 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.926_940delTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1 link	n.454-7940_454-7926delTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1 link	n.454-7940_454-7926delTGCTGCTGCTGCTGC	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ATXN8OS	ENST00000414504.6 link	n.1134_1148delTGCTGCTGCTGCTGC	splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	5
ENSG00000288330	ENST00000673087.1 link	n.34_48delCAGCAGCAGCAGCAG	non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000756272.1 link	n.799_813delTGCTGCTGCTGCTGC	non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.000211

AC:

AN:

109116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000206

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000267

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000153

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000293

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000266

AC:

AN:

349080

Hom.:

AF XY:

0.000285

AC XY:

AN XY:

186122

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000380

AC:

AN:

7904

American (AMR)

AF:

0.0000535

AC:

AN:

18688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11972

East Asian (EAS)

AF:

0.00

AC:

AN:

24792

South Asian (SAS)

AF:

0.000148

AC:

AN:

26956

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

21220

Middle Eastern (MID)

AF:

0.000635

AC:

AN:

1576

European-Non Finnish (NFE)

AF:

0.000296

AC:

AN:

216076

Other (OTH)

AF:

0.000503

AC:

AN:

19896

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.356

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000211

AC:

AN:

109116

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

AN XY:

52594

show subpopulations

African (AFR)

AF:

0.000206

AC:

AN:

24304

American (AMR)

AF:

0.00

AC:

AN:

10960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2848

East Asian (EAS)

AF:

0.000267

AC:

AN:

3746

South Asian (SAS)

AF:

0.00

AC:

AN:

3620

European-Finnish (FIN)

AF:

0.000153

AC:

AN:

6518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

256

European-Non Finnish (NFE)

AF:

0.000293

AC:

AN:

54686

Other (OTH)

AF:

0.00

AC:

AN:

1408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.19

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over