Variant 14-92071034-G-GC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_004993.6(ATXN3):c.891_892insG(p.Gln298AlafsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,601,550 control chromosomes in the GnomAD database, including 1,104 homozygotes. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. Q297Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.019 ( 63 hom., cov: 0)

Exomes 𝑓: 0.018 ( 1041 hom. )

Consequence

ATXN3
NM_004993.6 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.273

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 14-92071034-G-GC is Benign according to our data. Variant chr14-92071034-G-GC is described in ClinVar as [Benign]. Clinvar id is 3037422.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN3	NM_004993.6 linkuse as main transcript	c.891_892insG	p.Gln298AlafsTer20	frameshift_variant	10/11	ENST00000644486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN3	ENST00000644486.2 linkuse as main transcript	c.891_892insG	p.Gln298AlafsTer20	frameshift_variant	10/11		NM_004993.6	P1	P54252-2

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2845

AN:

151792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00352

Gnomad AMI

AF:

0.0374

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.0691

Gnomad SAS

AF:

0.0792

Gnomad FIN

AF:

0.0309

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0168

GnomAD3 exomes

AF:

0.0272

AC:

6712

AN:

246540

Hom.:

343

AF XY:

0.0292

AC XY:

3904

AN XY:

133650

show subpopulations

Gnomad AFR exome

AF:

0.00485

Gnomad AMR exome

AF:

0.00759

Gnomad ASJ exome

AF:

0.0240

Gnomad EAS exome

AF:

0.0613

Gnomad SAS exome

AF:

0.0676

Gnomad FIN exome

AF:

0.0323

Gnomad NFE exome

AF:

0.0191

Gnomad OTH exome

AF:

0.0271

GnomAD4 exome

AF:

0.0180

AC:

26105

AN:

1449640

Hom.:

1041

Cov.:

AF XY:

0.0197

AC XY:

14182

AN XY:

721328

show subpopulations

Gnomad4 AFR exome

AF:

0.00327

Gnomad4 AMR exome

AF:

0.00780

Gnomad4 ASJ exome

AF:

0.0239

Gnomad4 EAS exome

AF:

0.0916

Gnomad4 SAS exome

AF:

0.0647

Gnomad4 FIN exome

AF:

0.0329

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.0195

GnomAD4 genome

AF:

0.0187

AC:

2845

AN:

151910

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1502

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.00348

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.0268

Gnomad4 EAS

AF:

0.0688

Gnomad4 SAS

AF:

0.0799

Gnomad4 FIN

AF:

0.0309

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0294

Hom.:

Asia WGS

AF:

0.0660

AC:

228

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ATXN3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over