Variant chr14-92071010-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_004993.6(ATXN3):c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG(p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.039 ( 202 hom., cov: 20)

Exomes 𝑓: 0.034 ( 4293 hom. )

Failed GnomAD Quality Control

Consequence

ATXN3
NM_004993.6 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.168

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.

BP6

Variant 14-92071010-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG is Benign according to our data. Variant chr14-92071010-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG is described in ClinVar as [Benign]. Clinvar id is 218660.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0391 (5565/142438) while in subpopulation NFE AF= 0.0474 (3144/66386). AF 95% confidence interval is 0.046. There are 202 homozygotes in gnomad4. There are 2539 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

BS2

High AC in GnomAd4 at 5565 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN3	NM_004993.6 linkuse as main transcript	c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG	p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	conservative_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.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG	p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	conservative_inframe_insertion	10/11		NM_004993.6	ENSP00000496695.1		P54252-2

Frequencies

GnomAD3 genomes

AF:

0.0390

AC:

5555

AN:

142328

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0379

Gnomad AMI

AF:

0.0193

Gnomad AMR

AF:

0.0274

Gnomad ASJ

AF:

0.0223

Gnomad EAS

AF:

0.0248

Gnomad SAS

AF:

0.0318

Gnomad FIN

AF:

0.0229

Gnomad MID

AF:

0.0296

Gnomad NFE

AF:

0.0474

Gnomad OTH

AF:

0.0346

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0336

AC:

44006

AN:

1309066

Hom.:

4293

Cov.:

AF XY:

0.0340

AC XY:

22226

AN XY:

654526

show subpopulations

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.0208

Gnomad4 ASJ exome

AF:

0.0221

Gnomad4 EAS exome

AF:

0.0308

Gnomad4 SAS exome

AF:

0.0283

Gnomad4 FIN exome

AF:

0.0250

Gnomad4 NFE exome

AF:

0.0355

Gnomad4 OTH exome

AF:

0.0325

GnomAD4 genome

AF:

0.0391

AC:

5565

AN:

142438

Hom.:

202

Cov.:

AF XY:

0.0367

AC XY:

2539

AN XY:

69194

show subpopulations

Gnomad4 AFR

AF:

0.0381

Gnomad4 AMR

AF:

0.0273

Gnomad4 ASJ

AF:

0.0223

Gnomad4 EAS

AF:

0.0248

Gnomad4 SAS

AF:

0.0316

Gnomad4 FIN

AF:

0.0229

Gnomad4 NFE

AF:

0.0474

Gnomad4 OTH

AF:

0.0342

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

May 05, 2015

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

- -

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