13-70139383-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant names:

• chr13-70139383-A-ACTG
• rs193922930
• ENST00000673087.1:n.46_48dupCAG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000673087.1(ENSG00000288330):​n.46_48dupCAG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (15 hom., cov: 0)
  • Exomes 𝑓: 0.019 (210 hom.)
• Consequence: ENSG00000288330 ENST00000673087.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 0 publications found

Genes affected

ENSG00000288330 (HGNC:32925):

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0149 (1621/109110) while in subpopulation NFE AF = 0.0213 (1164/54662). AF 95% confidence interval is 0.0203. There are 15 homozygotes in GnomAd4. There are 760 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1621 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000673087.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN8OS	NR_002717.3		n.938_940dupTGC		non_coding_transcript_exon	Exon 5 of 5
	ATXN8OS	NR_185834.1		n.454-7928_454-7926dupTGC		intron	N/A
	ATXN8OS	NR_185835.1		n.454-7928_454-7926dupTGC		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000288330	ENST00000673087.1		n.46_48dupCAG		non_coding_transcript_exon	Exon 1 of 1
	ATXN8OS	ENST00000756272.1		n.811_813dupTGC		non_coding_transcript_exon	Exon 5 of 5
	ATXN8OS	ENST00000660386.1		n.451-7928_451-7926dupTGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 1623 AN: 109080 Hom.: 16 Cov.: 0

Gnomad AFR AF: 0.00770

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00492

Gnomad EAS AF: 0.00267

Gnomad SAS AF: 0.00470

Gnomad FIN AF: 0.00922

Gnomad MID AF: 0.0234

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0121

GnomAD4 exome AF: 0.0189 AC: 6570 AN: 348038 Hom.: 210 Cov.: 0 AF XY: 0.0184 AC XY: 3415 AN XY: 185566

African (AFR) AF: 0.0126 AC: 99 AN: 7888

American (AMR) AF: 0.0132 AC: 246 AN: 18626

Ashkenazi Jewish (ASJ) AF: 0.00879 AC: 105 AN: 11940

East Asian (EAS) AF: 0.00331 AC: 82 AN: 24776

South Asian (SAS) AF: 0.00832 AC: 224 AN: 26910

European-Finnish (FIN) AF: 0.00939 AC: 199 AN: 21186

Middle Eastern (MID) AF: 0.0191 AC: 30 AN: 1568

European-Non Finnish (NFE) AF: 0.0244 AC: 5244 AN: 215288

Other (OTH) AF: 0.0172 AC: 341 AN: 19856

GnomAD4 genome AF: 0.0149 AC: 1621 AN: 109110 Hom.: 15 Cov.: 0 AF XY: 0.0144 AC XY: 760 AN XY: 52644

African (AFR) AF: 0.00768 AC: 187 AN: 24360

American (AMR) AF: 0.0135 AC: 148 AN: 10968

Ashkenazi Jewish (ASJ) AF: 0.00492 AC: 14 AN: 2846

East Asian (EAS) AF: 0.00268 AC: 10 AN: 3730

South Asian (SAS) AF: 0.00471 AC: 17 AN: 3612

European-Finnish (FIN) AF: 0.00922 AC: 60 AN: 6510

Middle Eastern (MID) AF: 0.0169 AC: 4 AN: 236

European-Non Finnish (NFE) AF: 0.0213 AC: 1164 AN: 54662

Other (OTH) AF: 0.0120 AC: 17 AN: 1416

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs193922930; hg19: chr13-70713515;