14-92071009-C-CCCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM4 BP6_Moderate

The NM_004993.6(ATXN3):c.916_917insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGG(p.Gln305_Gly306insGluGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ATXN3 NM_004993.6 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.802

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_004993.6.
• BP6: Variant 14-92071009-C-CCCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT is Benign according to our data. Variant chr14-92071009-C-CCCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT is described in ClinVar as [Likely_benign]. Clinvar id is 3025693.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN3	NM_004993.6	c.916_917insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGG	p.Gln305_Gly306insGluGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	inframe_insertion	10/11	ENST00000644486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN3	ENST00000644486.2	c.916_917insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGG	p.Gln305_Gly306insGluGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	inframe_insertion	10/11		NM_004993.6	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

ATXN3: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-92537353;