chr3-63912684-G-GGCAGCA

Position:

chr3-63912684-G-GGCAGCA

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3BP6_ModerateBA1

The NM_001377405.1(ATXN7):c.113_118dupAGCAGC(p.Gln38_Gln39dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.106 in 1,086,078 control chromosomes in the GnomAD database, including 4,589 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.098 ( 776 hom., cov: 23)

Exomes 𝑓: 0.11 ( 3813 hom. )

Consequence

ATXN7
NM_001377405.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter U:1B: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 -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001377405.1

BP6

Variant 3-63912684-G-GGCAGCA is Benign according to our data. Variant chr3-63912684-G-GGCAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 402403.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN7	NM_001377405.1 linkuse as main transcript	c.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_inframe_insertion	3/13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1 linkuse as main transcript	c.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_inframe_insertion	2/13		NP_001170858.1	O15265-2
ATXN7	NM_000333.4 linkuse as main transcript	c.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_inframe_insertion	3/13		NP_000324.1	O15265-1Q9UPD8
ATXN7	NM_001377406.1 linkuse as main transcript	c.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_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.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_inframe_insertion	3/13		NM_001377405.1	ENSP00000501377.1		O15265-1

Frequencies

GnomAD3 genomes

AF:

0.0975

AC:

14097

AN:

144536

Hom.:

777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0617

Gnomad AMI

AF:

0.0408

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0626

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.0492

AC:

510

AN:

10356

Hom.:

AF XY:

0.0484

AC XY:

268

AN XY:

5542

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.0293

Gnomad ASJ exome

AF:

0.0320

Gnomad EAS exome

AF:

0.0294

Gnomad SAS exome

AF:

0.0233

Gnomad FIN exome

AF:

0.0459

Gnomad NFE exome

AF:

0.0731

Gnomad OTH exome

AF:

0.0350

GnomAD4 exome

AF:

0.107

AC:

100873

AN:

941440

Hom.:

3813

Cov.:

AF XY:

0.108

AC XY:

48317

AN XY:

446124

show subpopulations

Gnomad4 AFR exome

AF:

0.0584

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.117

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0559

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.0975

AC:

14106

AN:

144638

Hom.:

776

Cov.:

AF XY:

0.0960

AC XY:

6756

AN XY:

70368

show subpopulations

Gnomad4 AFR

AF:

0.0618

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.131

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.0626

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.117

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinal dystrophy

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2022

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Poly-Q expansions in this gene associated with spinocerebellar ataxia 7. SCA7 is characterized by progressive cerebellar ataxia, including dysarthria and dysphagia, and cone-rod and retinal dystrophy with progressive central visual loss resulting in blindness in affected adults. Onset in early childhood or infancy has an especially rapid and aggressive course often associated with failure to thrive and regression of motor milestones. Affected individuals usually have greater than 36 CAG repeats, although individuals with fewer repeats may also present with symptoms. -

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