13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTG

Position:

• chr13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Likely benign. Variant got -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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN8OS	NR_002717.3	n.926_940delTGCTGCTGCTGCTGC		non_coding_transcript_exon_variant	5/5
ATXN8OS	NR_185834.1	n.454-7940_454-7926delTGCTGCTGCTGCTGC		intron_variant
ATXN8OS	NR_185835.1	n.454-7940_454-7926delTGCTGCTGCTGCTGC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN8OS	ENST00000414504.6	n.1134_1148delTGCTGCTGCTGCTGC		splice_region_variant, non_coding_transcript_exon_variant	5/5	5
ENSG00000288330	ENST00000673087.1	n.34_48delCAGCAGCAGCAGCAG		non_coding_transcript_exon_variant	1/1
ATXN8OS	ENST00000660386.1	n.451-7940_451-7926delTGCTGCTGCTGCTGC		intron_variant

Frequencies

GnomAD3 genomes AF: 0.000211 AC: 23 AN: 109116 Hom.: 0 Cov.: 0

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: 93 AN: 349080 Hom.: 1 AF XY: 0.000285 AC XY: 53 AN XY: 186122

Gnomad4 AFR exome AF: 0.000380

Gnomad4 AMR exome AF: 0.0000535

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000148

Gnomad4 FIN exome AF: 0.000471

Gnomad4 NFE exome AF: 0.000296

Gnomad4 OTH exome AF: 0.000503

GnomAD4 genome AF: 0.000211 AC: 23 AN: 109116 Hom.: 0 Cov.: 0 AF XY: 0.000152 AC XY: 8 AN XY: 52594

Gnomad4 AFR AF: 0.000206

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000267

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000153

Gnomad4 NFE AF: 0.000293

Gnomad4 OTH AF: 0.00

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;