chr14-92071010-C-CTGCTGCTGCTGCTGCTGCTG

Position:

• chr14-92071010-C-CTGCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_004993.6(ATXN3):​c.915_916insCAGCAGCAGCAGCAGCAGCA​(p.Gly306fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.073 (575 hom., cov: 20)
  • Exomes 𝑓: 0.095 (6292 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATXN3 NM_004993.6 frameshift
• Clinical Significance: Benign no assertion criteria provided B:2
• 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 -9 ACMG points.

• BP6: Variant 14-92071010-C-CTGCTGCTGCTGCTGCTGCTG is Benign according to our data. Variant chr14-92071010-C-CTGCTGCTGCTGCTGCTGCTG is described in ClinVar as [Benign]. Clinvar id is 1209890.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN3	NM_004993.6	c.915_916insCAGCAGCAGCAGCAGCAGCA	p.Gly306fs	frameshift_variant	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_916insCAGCAGCAGCAGCAGCAGCA	p.Gly306fs	frameshift_variant	10/11		NM_004993.6	ENSP00000496695.1

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 10413 AN: 142368 Hom.: 576 Cov.: 20

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.0228

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.00259

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0691

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0947 AC: 124068 AN: 1310102 Hom.: 6292 Cov.: 92 AF XY: 0.0936 AC XY: 61338 AN XY: 655086

Gnomad4 AFR exome AF: 0.0182

Gnomad4 AMR exome AF: 0.0420

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.00115

Gnomad4 SAS exome AF: 0.0461

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0843

GnomAD4 genome AF: 0.0731 AC: 10413 AN: 142478 Hom.: 575 Cov.: 20 AF XY: 0.0748 AC XY: 5178 AN XY: 69224

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.00259

Gnomad4 SAS AF: 0.0459

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0683

Alfa AF: 0.225 Hom.: 51

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

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;