Genetic Variant ATXN3:p.Gln303_Gln305del (chr14-92071010-CCTGCTGCTG-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_004993.6(ATXN3):c.907_915delCAGCAGCAG(p.Gln303_Gln305del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 1,314,556 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATXN3
NM_004993.6 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.37

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Machado-Joseph disease
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
Machado-Joseph disease type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Machado-Joseph disease type 2
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Machado-Joseph disease type 3
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ATXN3 links:

ENSG00000303901 (HGNC:):

ENSG00000303901 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_004993.6

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN3	NM_004993.6 link	c.907_915delCAGCAGCAG	p.Gln303_Gln305del	conservative_inframe_deletion	Exon 10 of 11	ENST00000644486.2	NP_004984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN3	ENST00000644486.2 link	c.907_915delCAGCAGCAG	p.Gln303_Gln305del	conservative_inframe_deletion	Exon 10 of 11		NM_004993.6	ENSP00000496695.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

142396

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000228

AC:

AN:

1314556

Hom.:

AF XY:

0.00000152

AC XY:

AN XY:

657300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27564

American (AMR)

AF:

0.0000247

AC:

AN:

40510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24398

East Asian (EAS)

AF:

0.00

AC:

AN:

37452

South Asian (SAS)

AF:

0.00

AC:

AN:

79492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5148

European-Non Finnish (NFE)

AF:

0.00000201

AC:

AN:

995972

Other (OTH)

AF:

0.00

AC:

AN:

55108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

142396

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69104

African (AFR)

AF:

0.00

AC:

AN:

36200

American (AMR)

AF:

0.00

AC:

AN:

14398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3412

East Asian (EAS)

AF:

0.00

AC:

AN:

4642

South Asian (SAS)

AF:

0.00

AC:

AN:

4314

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66422

Other (OTH)

AF:

0.00

AC:

AN:

1940

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.4

Mutation Taster

=81/119

disease causing

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

14-92071010-CCTGCTGCTGCTG-CCTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over