14-92071010-C-CTG

Variant summary

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

The NM_004993.6(ATXN3):c.915_916insCA(p.Gly306GlnfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,456,906 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00013 (13 hom.)
• Consequence: ATXN3 NM_004993.6 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• 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	UniProt
ATXN3	NM_004993.6	c.915_916insCA	p.Gly306GlnfsTer26	frameshift_variant	10/11	ENST00000644486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN3	ENST00000644486.2	c.915_916insCA	p.Gly306GlnfsTer26	frameshift_variant	10/11		NM_004993.6	P1

Frequencies

GnomAD3 genomes AF: 0.0000140 AC: 2 AN: 142396 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000215

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000132 AC: 173 AN: 1314510 Hom.: 13 Cov.: 92 AF XY: 0.000152 AC XY: 100 AN XY: 657280

Gnomad4 AFR exome AF: 0.000218

Gnomad4 AMR exome AF: 0.0000247

Gnomad4 ASJ exome AF: 0.000328

Gnomad4 EAS exome AF: 0.0000267

Gnomad4 SAS exome AF: 0.000377

Gnomad4 FIN exome AF: 0.0000204

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.0000726

GnomAD4 genome AF: 0.0000140 AC: 2 AN: 142396 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 69104

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000215

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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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: rs1555397062; hg19: chr14-92537354;