3-63912684-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_001377405.1(ATXN7):c.107_118dupAGCAGCAGCAGC(p.Gln36_Gln39dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00351 in 1,087,064 control chromosomes in the GnomAD database, including 13 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 23)

Exomes 𝑓: 0.0036 ( 11 hom. )

Consequence

ATXN7
NM_001377405.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B: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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001377405.1

BP6

Variant 3-63912684-G-GGCAGCAGCAGCA is Benign according to our data. Variant chr3-63912684-G-GGCAGCAGCAGCA is described in ClinVar as Benign. ClinVar VariationId is 2653938.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 461 AD gene.

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.107_118dupAGCAGCAGCAGC	p.Gln36_Gln39dup	disruptive_inframe_insertion	Exon 3 of 13	NP_001364334.1	O15265-1
ATXN7	NM_001177387.1		c.107_118dupAGCAGCAGCAGC	p.Gln36_Gln39dup	disruptive_inframe_insertion	Exon 2 of 13	NP_001170858.1	O15265-2
ATXN7	NM_000333.4		c.107_118dupAGCAGCAGCAGC	p.Gln36_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.107_118dupAGCAGCAGCAGC	p.Gln36_Gln39dup	disruptive_inframe_insertion	Exon 3 of 13	ENSP00000501377.1	O15265-1
ATXN7	ENST00000295900.10	TSL:1	c.107_118dupAGCAGCAGCAGC	p.Gln36_Gln39dup	disruptive_inframe_insertion	Exon 3 of 13	ENSP00000295900.6	O15265-1
ATXN7	ENST00000522345.2	TSL:2	c.107_118dupAGCAGCAGCAGC	p.Gln36_Gln39dup	disruptive_inframe_insertion	Exon 1 of 12	ENSP00000428067.2	O15265-2

Frequencies

GnomAD3 genomes

AF:

0.00318

AC:

460

AN:

144612

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.000593

Gnomad EAS

AF:

0.00167

Gnomad SAS

AF:

0.00892

Gnomad FIN

AF:

0.00153

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00339

Gnomad OTH

AF:

0.00598

GnomAD2 exomes

AF:

0.00232

AC:

AN:

10356

AF XY:

0.00198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00291

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00298

Gnomad NFE exome

AF:

0.00205

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00356

AC:

3355

AN:

942350

Hom.:

Cov.:

AF XY:

0.00360

AC XY:

1608

AN XY:

446544

show subpopulations

African (AFR)

AF:

0.00237

AC:

AN:

17714

American (AMR)

AF:

0.00341

AC:

AN:

5282

Ashkenazi Jewish (ASJ)

AF:

0.00167

AC:

AN:

8400

East Asian (EAS)

AF:

0.00125

AC:

AN:

9614

South Asian (SAS)

AF:

0.00944

AC:

189

AN:

20020

European-Finnish (FIN)

AF:

0.00339

AC:

AN:

18854

Middle Eastern (MID)

AF:

0.000477

AC:

AN:

2096

European-Non Finnish (NFE)

AF:

0.00349

AC:

2889

AN:

827268

Other (OTH)

AF:

0.00381

AC:

126

AN:

33102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

141

282

424

565

706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<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:

0.00319

AC:

461

AN:

144714

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

243

AN XY:

70410

show subpopulations

African (AFR)

AF:

0.00218

AC:

AN:

39998

American (AMR)

AF:

0.00510

AC:

AN:

14698

Ashkenazi Jewish (ASJ)

AF:

0.000593

AC:

AN:

3374

East Asian (EAS)

AF:

0.00168

AC:

AN:

4766

South Asian (SAS)

AF:

0.00892

AC:

AN:

4708

European-Finnish (FIN)

AF:

0.00153

AC:

AN:

8512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00339

AC:

222

AN:

65440

Other (OTH)

AF:

0.00591

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000716

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.1

Mutation Taster

=68/32

polymorphism

(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