Variant 14-92071020-C-CTGCTGCTGCTGCTGT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

The NM_001164778.2(ATXN3):c.406_420dupACAGCAGCAGCAGCA(p.Ala140_Ala141insThrAlaAlaAlaAla) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000997 in 1,607,440 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0053 ( 22 hom., cov: 35)

Exomes 𝑓: 0.00055 ( 24 hom. )

Consequence

ATXN3
NM_001164778.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.86

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:

ATXN3 (HGNC:):

ATXN3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001164778.2

BP6

Variant 14-92071020-C-CTGCTGCTGCTGCTGT is Benign according to our data. Variant chr14-92071020-C-CTGCTGCTGCTGCTGT is described in ClinVar as [Benign]. Clinvar id is 3044058.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00526 (798/151722) while in subpopulation AFR AF= 0.0186 (766/41176). AF 95% confidence interval is 0.0175. There are 22 homozygotes in gnomad4. There are 383 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High AC in GnomAd4 at 798 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN3	NM_004993.6 linkuse as main transcript	c.891_905dupACAGCAGCAGCAGCA	p.Gln298_Gln302dup	disruptive_inframe_insertion	10/11	ENST00000644486.2	NP_004984.2	P54252-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN3	ENST00000644486.2 linkuse as main transcript	c.891_905dupACAGCAGCAGCAGCA	p.Gln298_Gln302dup	disruptive_inframe_insertion	10/11		NM_004993.6	ENSP00000496695.1		P54252-2

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

795

AN:

151604

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00288

GnomAD4 exome

AF:

0.000552

AC:

804

AN:

1455718

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

350

AN XY:

724060

show subpopulations

Gnomad4 AFR exome

AF:

0.0200

Gnomad4 AMR exome

AF:

0.000632

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000198

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00526

AC:

798

AN:

151722

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

383

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.0186

Gnomad4 AMR

AF:

0.00145

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.000772

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATXN3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 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

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