chr14-92071010-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Position:

• chr14-92071010-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_004993.6(ATXN3):​c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG​(p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) variant causes a inframe insertion 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 0.014 (115 hom., cov: 20)
  • Exomes 𝑓: 0.0025 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATXN3 NM_004993.6 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

Genes affected

ATXN3 (HGNC:7106): (ataxin 3) Machado-Joseph disease, also known as spinocerebellar ataxia-3, is an autosomal dominant neurologic disorder. The protein encoded by this gene contains (CAG)n repeats in the coding region, and the expansion of these repeats from the normal 12-44 to 52-86 is one cause of Machado-Joseph disease. There is a negative correlation between the age of onset and CAG repeat numbers. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN3	NM_004993.6	c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG	p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	inframe_insertion	10/11	ENST00000644486.2	NP_004984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN3	ENST00000644486.2	c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG	p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	inframe_insertion	10/11		NM_004993.6	ENSP00000496695	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2002 AN: 142284 Hom.: 115 Cov.: 20 FAILED QC

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00757

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000431

Gnomad SAS AF: 0.00696

Gnomad FIN AF: 0.00172

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.00649

Gnomad OTH AF: 0.0134

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00246 AC: 3234 AN: 1314292 Hom.: 1 Cov.: 92 AF XY: 0.00250 AC XY: 1643 AN XY: 657158

Gnomad4 AFR exome AF: 0.0182

Gnomad4 AMR exome AF: 0.00284

Gnomad4 ASJ exome AF: 0.000164

Gnomad4 EAS exome AF: 0.000748

Gnomad4 SAS exome AF: 0.00404

Gnomad4 FIN exome AF: 0.00106

Gnomad4 NFE exome AF: 0.00196

Gnomad4 OTH exome AF: 0.00461

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0141 AC: 2006 AN: 142394 Hom.: 115 Cov.: 20 AF XY: 0.0130 AC XY: 901 AN XY: 69186

Gnomad4 AFR AF: 0.0384

Gnomad4 AMR AF: 0.00756

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000432

Gnomad4 SAS AF: 0.00673

Gnomad4 FIN AF: 0.00172

Gnomad4 NFE AF: 0.00649

Gnomad4 OTH AF: 0.0133

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: rs193922928; hg19: chr14-92537354;