rs17807815

chr14-92089711-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004993.6(ATXN3):c.388-894A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 152,258 control chromosomes in the GnomAD database, including 588 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.077 (588 hom., cov: 32)
• Consequence: ATXN3 NM_004993.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN3	NM_004993.6	c.388-894A>G		intron_variant		ENST00000644486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN3	ENST00000644486.2	c.388-894A>G		intron_variant			NM_004993.6	P1

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11663 AN: 152140 Hom.: 583 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.0831

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0767 AC: 11685 AN: 152258 Hom.: 588 Cov.: 32 AF XY: 0.0766 AC XY: 5705 AN XY: 74450

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0261

Gnomad4 SAS AF: 0.0844

Gnomad4 FIN AF: 0.0619

Gnomad4 NFE AF: 0.0991

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0981 Hom.: 753

Bravo AF: 0.0782

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs17807815; hg19: chr14-92556055;