Variant 3-63912684-G-GGCAGCAGCAGCAGCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_001377405.1(ATXN7):c.104_118dup(p.Gln35_Gln39dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00144 in 144,718 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00083 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

ATXN7
NM_001377405.1 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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 Benign. Variant got -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001377405.1

BP6

Variant 3-63912684-G-GGCAGCAGCAGCAGCA is Benign according to our data. Variant chr3-63912684-G-GGCAGCAGCAGCAGCA is described in ClinVar as [Benign]. Clinvar id is 2653939.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 209 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATXN7	NM_001377405.1 linkuse as main transcript	c.104_118dup	p.Gln35_Gln39dup	inframe_insertion	3/13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_000333.4 linkuse as main transcript	c.104_118dup	p.Gln35_Gln39dup	inframe_insertion	3/13		NP_000324.1
ATXN7	NM_001177387.1 linkuse as main transcript	c.104_118dup	p.Gln35_Gln39dup	inframe_insertion	2/13		NP_001170858.1
ATXN7	NM_001377406.1 linkuse as main transcript	c.104_118dup	p.Gln35_Gln39dup	inframe_insertion	2/12		NP_001364335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7	ENST00000674280.1 linkuse as main transcript	c.104_118dup	p.Gln35_Gln39dup	inframe_insertion	3/13		NM_001377405.1	ENSP00000501377	P2	O15265-1

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

208

AN:

144616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00293

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.00105

Gnomad SAS

AF:

0.00106

Gnomad FIN

AF:

0.000235

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00199

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000826

AC:

778

AN:

942100

Hom.:

Cov.:

AF XY:

0.000820

AC XY:

366

AN XY:

446440

show subpopulations

Gnomad4 AFR exome

AF:

0.00113

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.000238

Gnomad4 EAS exome

AF:

0.00312

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.000424

Gnomad4 NFE exome

AF:

0.000791

Gnomad4 OTH exome

AF:

0.000937

GnomAD4 genome

AF:

0.00144

AC:

209

AN:

144718

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

AN XY:

70412

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00292

Gnomad4 ASJ

AF:

0.000296

Gnomad4 EAS

AF:

0.00105

Gnomad4 SAS

AF:

0.00106

Gnomad4 FIN

AF:

0.000235

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00197

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

ATXN7: BS1, BS2 -

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over