13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Position:

• chr13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Benign. Variant got -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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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]

ENSG00000288330 (HGNC:32925):

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN8OS	NR_002717.3	n.938_940delTGC		non_coding_transcript_exon_variant	5/5
ATXN8OS	NR_185834.1	n.454-7928_454-7926delTGC		intron_variant
ATXN8OS	NR_185835.1	n.454-7928_454-7926delTGC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN8OS	ENST00000414504.6	n.1146_1148delTGC		splice_region_variant, non_coding_transcript_exon_variant	5/5	5
ENSG00000288330	ENST00000673087.1	n.46_48delCAG		non_coding_transcript_exon_variant	1/1
ATXN8OS	ENST00000660386.1	n.451-7928_451-7926delTGC		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 2729 AN: 108972 Hom.: 33 Cov.: 0

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

Gnomad4 AFR exome AF: 0.0303

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.00843

Gnomad4 EAS exome AF: 0.0296

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.0147

Gnomad4 NFE exome AF: 0.0227

Gnomad4 OTH exome AF: 0.0234

GnomAD4 genome AF: 0.0251 AC: 2731 AN: 109002 Hom.: 33 Cov.: 0 AF XY: 0.0250 AC XY: 1313 AN XY: 52588

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.0102

Gnomad4 EAS AF: 0.0209

Gnomad4 SAS AF: 0.0599

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.0244

Gnomad4 OTH AF: 0.0290

ClinVar

Not reported in ClinVar

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: rs193922930; hg19: chr13-70713515;