chr14-92071010-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Position:

• chr14-92071010-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004993.6(ATXN3):​c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG​(p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) variant causes a conservative 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 0.038 (244 hom., cov: 20)
  • Exomes 𝑓: 0.010 (26 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATXN3 NM_004993.6 conservative_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]

ATXN3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN3	NM_004993.6	c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG	p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	conservative_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_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG	p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	conservative_inframe_insertion	10/11		NM_004993.6	ENSP00000496695.1

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5400 AN: 142228 Hom.: 243 Cov.: 20

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00646

Gnomad SAS AF: 0.00997

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.0362

Gnomad NFE AF: 0.0330

Gnomad OTH AF: 0.0253

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0103 AC: 13556 AN: 1314342 Hom.: 26 Cov.: 92 AF XY: 0.0103 AC XY: 6793 AN XY: 657192

Gnomad4 AFR exome AF: 0.0238

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.00569

Gnomad4 SAS exome AF: 0.00637

Gnomad4 FIN exome AF: 0.0370

Gnomad4 NFE exome AF: 0.00881

Gnomad4 OTH exome AF: 0.0149

GnomAD4 genome AF: 0.0380 AC: 5413 AN: 142338 Hom.: 244 Cov.: 20 AF XY: 0.0367 AC XY: 2537 AN XY: 69160

Gnomad4 AFR AF: 0.0566

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.00647

Gnomad4 SAS AF: 0.00998

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.0330

Gnomad4 OTH AF: 0.0255

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;