3-63912684-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia 7
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
spinocerebellar ataxia type 7
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

ATXN7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377405.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN7	NM_001377405.1	MANE Select	c.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_inframe_insertion	Exon 3 of 13	NP_001364334.1	O15265-1
ATXN7	NM_001177387.1		c.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_inframe_insertion	Exon 2 of 13	NP_001170858.1	O15265-2
ATXN7	NM_000333.4		c.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_inframe_insertion	Exon 3 of 13	NP_000324.1	O15265-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN7	ENST00000674280.1	MANE Select	c.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_inframe_insertion	Exon 3 of 13	ENSP00000501377.1	O15265-1
ATXN7	ENST00000295900.10	TSL:1	c.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_inframe_insertion	Exon 3 of 13	ENSP00000295900.6	O15265-1
ATXN7	ENST00000522345.2	TSL:2	c.113_118dupAGCAGC	p.Gln38_Gln39dup	disruptive_inframe_insertion	Exon 1 of 12	ENSP00000428067.2	O15265-2

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

GnomAD2 exomes

AF:

0.0492

AC:

510

AN:

10356

AF XY:

0.0484

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 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

African (AFR)

AF:

0.0584

AC:

1034

AN:

17710

American (AMR)

AF:

0.184

AC:

971

AN:

5268

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

1003

AN:

8386

East Asian (EAS)

AF:

0.117

AC:

1124

AN:

9606

South Asian (SAS)

AF:

0.114

AC:

2272

AN:

20006

European-Finnish (FIN)

AF:

0.0559

AC:

1053

AN:

18832

Middle Eastern (MID)

AF:

0.153

AC:

321

AN:

2096

European-Non Finnish (NFE)

AF:

0.108

AC:

89406

AN:

826458

Other (OTH)

AF:

0.112

AC:

3689

AN:

33078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

4510

9020

13529

18039

22549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4224

8448

12672

16896

21120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0975

AC:

14106

AN:

144638

Hom.:

776

Cov.:

AF XY:

0.0960

AC XY:

6756

AN XY:

70368

show subpopulations

African (AFR)

AF:

0.0618

AC:

2473

AN:

39986

American (AMR)

AF:

0.137

AC:

2015

AN:

14688

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

409

AN:

3372

East Asian (EAS)

AF:

0.131

AC:

625

AN:

4762

South Asian (SAS)

AF:

0.108

AC:

509

AN:

4704

European-Finnish (FIN)

AF:

0.0626

AC:

532

AN:

8502

Middle Eastern (MID)

AF:

0.202

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.110

AC:

7211

AN:

65406

Other (OTH)

AF:

0.117

AC:

238

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

611

1221

1832

2442

3053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0284

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.1

Mutation Taster

=68/32

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over