14-92071010-C-CCTGCTGCTGCTGCTG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004993.6(ATXN3):c.915_916insCAGCAGCAGCAGCAG(p.Gln301_Gln305dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (11 hom., cov: 20)
  • Exomes 𝑓: 0.0010 (33 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATXN3 NM_004993.6 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.168

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 14-92071010-C-CCTGCTGCTGCTGCTG is Benign according to our data. Variant chr14-92071010-C-CCTGCTGCTGCTGCTG is described in ClinVar as [Benign]. Clinvar id is 2644469.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 468 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN3	NM_004993.6	c.915_916insCAGCAGCAGCAGCAG	p.Gln301_Gln305dup	inframe_insertion	10/11	ENST00000644486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN3	ENST00000644486.2	c.915_916insCAGCAGCAGCAGCAG	p.Gln301_Gln305dup	inframe_insertion	10/11		NM_004993.6	P1

Frequencies

GnomAD3 genomes AF: 0.00329 AC: 468 AN: 142394 Hom.: 11 Cov.: 20

Gnomad AFR AF: 0.00928

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00234

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000927

Gnomad FIN AF: 0.000304

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.000933

Gnomad OTH AF: 0.00155

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00104 AC: 1369 AN: 1314286 Hom.: 33 Cov.: 92 AF XY: 0.00104 AC XY: 684 AN XY: 657180

Gnomad4 AFR exome AF: 0.0104

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.000736

Gnomad4 NFE exome AF: 0.000749

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00330 AC: 470 AN: 142504 Hom.: 11 Cov.: 20 AF XY: 0.00341 AC XY: 236 AN XY: 69232

Gnomad4 AFR AF: 0.00931

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.00234

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000928

Gnomad4 FIN AF: 0.000304

Gnomad4 NFE AF: 0.000934

Gnomad4 OTH AF: 0.00153

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

ATXN3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs193922928; hg19: chr14-92537354;