Variant 3-63912684-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3

The NM_001377405.1(ATXN7):c.118_119insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC(p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000277 in 144,616 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0000053 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATXN7
NM_001377405.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.10

Variant links:

Genes affected

ATXN7 (HGNC:10560): (ataxin 7) The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the 'pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. This locus has been mapped to chromosome 3, and it has been determined that the diseased allele associated with spinocerebellar ataxia-7 contains 37-306 CAG repeats (near the N-terminus), compared to 4-35 in the normal allele. The encoded protein is a component of the SPT3/TAF9/GCN5 acetyltransferase (STAGA) and TBP-free TAF-containing (TFTC) chromatin remodeling complexes, and it thus plays a role in transcriptional regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ATXN7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_001377405.1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN7	NM_001377405.1 link	c.118_119insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC	p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	3/13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1 link	c.118_119insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC	p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	2/13		NP_001170858.1	O15265-2
ATXN7	NM_000333.4 link	c.118_119insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC	p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	3/13		NP_000324.1	O15265-1Q9UPD8
ATXN7	NM_001377406.1 link	c.118_119insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC	p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	2/12		NP_001364335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7	ENST00000674280.1 link	c.118_119insAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC	p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	3/13		NM_001377405.1	ENSP00000501377.1		O15265-1

Frequencies

GnomAD3 genomes

AF:

0.0000277

AC:

AN:

144616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000501

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000531

AC:

AN:

942434

Hom.:

Cov.:

AF XY:

0.00000672

AC XY:

AN XY:

446588

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000159

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000604

GnomAD4 genome

AF:

0.0000277

AC:

AN:

144616

Hom.:

Cov.:

AF XY:

0.0000285

AC XY:

AN XY:

70298

show subpopulations

Gnomad4 AFR

AF:

0.0000501

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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