chr14-92071010-C-CCTGCTGCTGCTGCTGCTG

Position:

• chr14-92071010-C-CCTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004993.6(ATXN3):​c.915_916insCAGCAGCAGCAGCAGCAG​(p.Gln300_Gln305dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0047 (11 hom., cov: 20)
  • Exomes 𝑓: 0.0046 (232 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATXN3 NM_004993.6 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• 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 -4 ACMG points.

• BS2: High AC in GnomAd4 at 668 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN3	NM_004993.6	c.915_916insCAGCAGCAGCAGCAGCAG	p.Gln300_Gln305dup	inframe_insertion	10/11	ENST00000644486.2	NP_004984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN3	ENST00000644486.2	c.915_916insCAGCAGCAGCAGCAGCAG	p.Gln300_Gln305dup	inframe_insertion	10/11		NM_004993.6	ENSP00000496695	P1

Frequencies

GnomAD3 genomes AF: 0.00471 AC: 670 AN: 142388 Hom.: 11 Cov.: 20

Gnomad AFR AF: 0.00713

Gnomad AMI AF: 0.00682

Gnomad AMR AF: 0.00319

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000464

Gnomad FIN AF: 0.00739

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00411

Gnomad OTH AF: 0.00619

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00460 AC: 6047 AN: 1314098 Hom.: 232 Cov.: 92 AF XY: 0.00447 AC XY: 2935 AN XY: 657034

Gnomad4 AFR exome AF: 0.00842

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.000328

Gnomad4 EAS exome AF: 0.000107

Gnomad4 SAS exome AF: 0.000869

Gnomad4 FIN exome AF: 0.00564

Gnomad4 NFE exome AF: 0.00508

Gnomad4 OTH exome AF: 0.00505

GnomAD4 genome AF: 0.00469 AC: 668 AN: 142498 Hom.: 11 Cov.: 20 AF XY: 0.00449 AC XY: 311 AN XY: 69230

Gnomad4 AFR AF: 0.00708

Gnomad4 AMR AF: 0.00319

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000464

Gnomad4 FIN AF: 0.00739

Gnomad4 NFE AF: 0.00410

Gnomad4 OTH AF: 0.00612

ClinVar

Not reported in ClinVar

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;