Genetic Variant ATXN8OS:n.1146_1148delTGC (chr13-70139383-ACTG-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000414504.6(ATXN8OS):n.1146_1148delTGC 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 0.0239 in 454,152 control chromosomes in the GnomAD database, including 199 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.025 ( 33 hom., cov: 0)

Exomes 𝑓: 0.024 ( 166 hom. )

Consequence

ATXN8OS
ENST00000414504.6 splice_region, non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.420

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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATXN8OS	NR_002717.3 link	n.938_940delTGC	non_coding_transcript_exon_variant	Exon 5 of 5
ATXN8OS	NR_185834.1 link	n.454-7928_454-7926delTGC	intron_variant	Intron 3 of 4
ATXN8OS	NR_185835.1 link	n.454-7928_454-7926delTGC	intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ATXN8OS	ENST00000414504.6 link	n.1146_1148delTGC	splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	5
ENSG00000288330	ENST00000673087.1 link	n.46_48delCAG	non_coding_transcript_exon_variant	Exon 1 of 1
ATXN8OS	ENST00000756272.1 link	n.811_813delTGC	non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

2729

AN:

108972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.0195

Gnomad AMR

AF:

0.0271

Gnomad ASJ

AF:

0.0102

Gnomad EAS

AF:

0.0208

Gnomad SAS

AF:

0.0595

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.0508

Gnomad NFE

AF:

0.0244

Gnomad OTH

AF:

0.0278

GnomAD4 exome

AF:

0.0235

AC:

8119

AN:

345150

Hom.:

166

AF XY:

0.0243

AC XY:

4461

AN XY:

183850

show subpopulations

African (AFR)

AF:

0.0303

AC:

237

AN:

7820

American (AMR)

AF:

0.0143

AC:

261

AN:

18260

Ashkenazi Jewish (ASJ)

AF:

0.00843

AC:

100

AN:

11866

East Asian (EAS)

AF:

0.0296

AC:

731

AN:

24668

South Asian (SAS)

AF:

0.0420

AC:

1104

AN:

26268

European-Finnish (FIN)

AF:

0.0147

AC:

310

AN:

21046

Middle Eastern (MID)

AF:

0.0397

AC:

AN:

1560

European-Non Finnish (NFE)

AF:

0.0227

AC:

4853

AN:

213930

Other (OTH)

AF:

0.0234

AC:

461

AN:

19732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

278

556

835

1113

1391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.0251

AC:

2731

AN:

109002

Hom.:

Cov.:

AF XY:

0.0250

AC XY:

1313

AN XY:

52588

show subpopulations

African (AFR)

AF:

0.0260

AC:

633

AN:

24308

American (AMR)

AF:

0.0271

AC:

297

AN:

10964

Ashkenazi Jewish (ASJ)

AF:

0.0102

AC:

AN:

2848

East Asian (EAS)

AF:

0.0209

AC:

AN:

3726

South Asian (SAS)

AF:

0.0599

AC:

216

AN:

3606

European-Finnish (FIN)

AF:

0.0118

AC:

AN:

6510

Middle Eastern (MID)

AF:

0.0466

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0244

AC:

1334

AN:

54622

Other (OTH)

AF:

0.0290

AC:

AN:

1412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

102

204

305

407

509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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

-0.42

Splicing

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

Publications

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13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

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