ENST00000414504.6:n.1143_1148delTGCTGC

Variant names:

• chr13-70139383-ACTGCTG-A
• rs193922930
• ENST00000414504.6:n.1143_1148delTGCTGC

Variant summary

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

The ENST00000414504.6(ATXN8OS):​n.1143_1148delTGCTGC 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 0.186 in 440,074 control chromosomes in the GnomAD database, including 4,669 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (2441 hom., cov: 0)
  • Exomes 𝑓: 0.18 (2228 hom.)
• Consequence: ATXN8OS ENST00000414504.6 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 0 publications found

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

ENSG00000288330 (HGNC:32925):

ACMG classification

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

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000414504.6. 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.935_940delTGCTGC		non_coding_transcript_exon	Exon 5 of 5
	ATXN8OS	NR_185834.1		n.454-7931_454-7926delTGCTGC		intron	N/A
	ATXN8OS	NR_185835.1		n.454-7931_454-7926delTGCTGC		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN8OS	ENST00000414504.6	TSL:5	n.1143_1148delTGCTGC		splice_region non_coding_transcript_exon	Exon 5 of 5
	ENSG00000288330	ENST00000673087.1		n.43_48delCAGCAG		non_coding_transcript_exon	Exon 1 of 1
	ATXN8OS	ENST00000756272.1		n.808_813delTGCTGC		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 23473 AN: 108134 Hom.: 2439 Cov.: 0

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.175 AC: 58169 AN: 331902 Hom.: 2228 AF XY: 0.173 AC XY: 30489 AN XY: 175910

African (AFR) AF: 0.0552 AC: 432 AN: 7826

American (AMR) AF: 0.134 AC: 2286 AN: 17012

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 2243 AN: 11364

East Asian (EAS) AF: 0.104 AC: 2537 AN: 24432

South Asian (SAS) AF: 0.172 AC: 4051 AN: 23586

European-Finnish (FIN) AF: 0.170 AC: 3507 AN: 20640

Middle Eastern (MID) AF: 0.211 AC: 324 AN: 1532

European-Non Finnish (NFE) AF: 0.189 AC: 39058 AN: 206406

Other (OTH) AF: 0.195 AC: 3731 AN: 19104

GnomAD4 genome AF: 0.217 AC: 23482 AN: 108172 Hom.: 2441 Cov.: 0 AF XY: 0.217 AC XY: 11304 AN XY: 52162

African (AFR) AF: 0.0735 AC: 1783 AN: 24262

American (AMR) AF: 0.248 AC: 2678 AN: 10812

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 752 AN: 2834

East Asian (EAS) AF: 0.109 AC: 405 AN: 3724

South Asian (SAS) AF: 0.351 AC: 1252 AN: 3570

European-Finnish (FIN) AF: 0.209 AC: 1343 AN: 6428

Middle Eastern (MID) AF: 0.267 AC: 62 AN: 232

European-Non Finnish (NFE) AF: 0.271 AC: 14650 AN: 54148

Other (OTH) AF: 0.241 AC: 337 AN: 1398

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19

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;