13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTG

Position:

• chr13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000414504.6(ATXN8OS):​n.1137_1148delTGCTGCTGCTGC 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 0.000585 in 458,136 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00093 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00048 (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 102 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN8OS	NR_002717.3	n.929_940delTGCTGCTGCTGC		non_coding_transcript_exon_variant	5/5
ATXN8OS	NR_185834.1	n.454-7937_454-7926delTGCTGCTGCTGC		intron_variant
ATXN8OS	NR_185835.1	n.454-7937_454-7926delTGCTGCTGCTGC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN8OS	ENST00000414504.6	n.1137_1148delTGCTGCTGCTGC		splice_region_variant, non_coding_transcript_exon_variant	5/5	5
ENSG00000288330	ENST00000673087.1	n.37_48delCAGCAGCAGCAG		non_coding_transcript_exon_variant	1/1
ATXN8OS	ENST00000660386.1	n.451-7937_451-7926delTGCTGCTGCTGC		intron_variant

Frequencies

GnomAD3 genomes AF: 0.000917 AC: 100 AN: 109110 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000182

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000153

Gnomad MID AF: 0.00391

Gnomad NFE AF: 0.000183

Gnomad OTH AF: 0.000710

GnomAD4 exome AF: 0.000476 AC: 166 AN: 348996 Hom.: 1 AF XY: 0.000398 AC XY: 74 AN XY: 186086

Gnomad4 AFR exome AF: 0.00533

Gnomad4 AMR exome AF: 0.00129

Gnomad4 ASJ exome AF: 0.00167

Gnomad4 EAS exome AF: 0.000444

Gnomad4 SAS exome AF: 0.000668

Gnomad4 FIN exome AF: 0.000141

Gnomad4 NFE exome AF: 0.000180

Gnomad4 OTH exome AF: 0.000453

GnomAD4 genome AF: 0.000935 AC: 102 AN: 109140 Hom.: 1 Cov.: 0 AF XY: 0.00114 AC XY: 60 AN XY: 52662

Gnomad4 AFR AF: 0.00357

Gnomad4 AMR AF: 0.000182

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000153

Gnomad4 NFE AF: 0.000183

Gnomad4 OTH AF: 0.000706

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;