Variant 14-92071010-CCTGCTG-CCTG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_004993.6(ATXN3):c.913_915del(p.Gln305del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 1,448,172 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

ATXN3
NM_004993.6 inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.902

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 Likely_benign. Variant got -5 ACMG points.

BP6

Variant 14-92071010-CCTG-C is Benign according to our data. Variant chr14-92071010-CCTG-C is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN3	NM_004993.6 linkuse as main transcript	c.913_915del	p.Gln305del	inframe_deletion	10/11	ENST00000644486.2	NP_004984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN3	ENST00000644486.2 linkuse as main transcript	c.913_915del	p.Gln305del	inframe_deletion	10/11		NM_004993.6	ENSP00000496695	P1	P54252-2

Frequencies

GnomAD3 genomes

AF:

0.0000351

AC:

AN:

142386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000829

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:

0.0000301

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000666

AC:

AN:

1305786

Hom.:

AF XY:

0.0000674

AC XY:

AN XY:

652944

show subpopulations

Gnomad4 AFR exome

AF:

0.000146

Gnomad4 AMR exome

AF:

0.000125

Gnomad4 ASJ exome

AF:

0.0000412

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.000101

Gnomad4 FIN exome

AF:

0.000391

Gnomad4 NFE exome

AF:

0.0000465

Gnomad4 OTH exome

AF:

0.0000548

GnomAD4 genome

AF:

0.0000351

AC:

AN:

142386

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

69096

show subpopulations

Gnomad4 AFR

AF:

0.0000829

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000301

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over