ENST00000414504.6:n.1013G>T

Variant names:

• chr13-70139294-G-T
• rs17751306
• ENST00000414504.6:n.1013G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The ENST00000414504.6(ATXN8OS):​n.1013G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 376,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: ATXN8OS ENST00000414504.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• 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

ATXN8 (HGNC:32925):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN8OS	NR_002717.3		n.805G>T		non_coding_transcript_exon	Exon 5 of 5
	ATXN8OS	NR_185834.1		n.454-8061G>T		intron	N/A
	ATXN8OS	NR_185835.1		n.454-8061G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN8OS	ENST00000414504.6	TSL:5	n.1013G>T		non_coding_transcript_exon	Exon 5 of 5
	ATXN8	ENST00000673087.1		n.138C>A		non_coding_transcript_exon	Exon 1 of 1
	ATXN8OS	ENST00000756272.1		n.678G>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000133 AC: 5 AN: 376950 Hom.: 0 Cov.: 0 AF XY: 0.0000100 AC XY: 2 AN XY: 199242

African (AFR) AF: 0.00 AC: 0 AN: 10508

American (AMR) AF: 0.00 AC: 0 AN: 18200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13222

East Asian (EAS) AF: 0.00 AC: 0 AN: 28328

South Asian (SAS) AF: 0.00 AC: 0 AN: 25346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1720

European-Non Finnish (NFE) AF: 0.0000216 AC: 5 AN: 231932

Other (OTH) AF: 0.00 AC: 0 AN: 22022

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.080
DANN	Benign	0.56
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs17751306; hg19: chr13-70713426;