chr3-63912714-A-AGCC

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.123_125dupGCC(p.Pro42dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,212,028 control chromosomes in the GnomAD database, including 39 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0079 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0074 ( 31 hom. )

Consequence

ATXN7
NM_001377405.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.825

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: G2P, Labcorp Genetics (formerly Invitae)
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 3-63912714-A-AGCC is Benign according to our data. Variant chr3-63912714-A-AGCC is described in ClinVar as Benign. ClinVar VariationId is 2653941.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1164 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.123_125dupGCC	p.Pro42dup	disruptive_inframe_insertion	Exon 3 of 13	NP_001364334.1	O15265-1
ATXN7	NM_001177387.1		c.123_125dupGCC	p.Pro42dup	disruptive_inframe_insertion	Exon 2 of 13	NP_001170858.1	O15265-2
ATXN7	NM_000333.4		c.123_125dupGCC	p.Pro42dup	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.123_125dupGCC	p.Pro42dup	disruptive_inframe_insertion	Exon 3 of 13	ENSP00000501377.1	O15265-1
ATXN7	ENST00000295900.10	TSL:1	c.123_125dupGCC	p.Pro42dup	disruptive_inframe_insertion	Exon 3 of 13	ENSP00000295900.6	O15265-1
ATXN7	ENST00000522345.2	TSL:2	c.123_125dupGCC	p.Pro42dup	disruptive_inframe_insertion	Exon 1 of 12	ENSP00000428067.2	O15265-2

Frequencies

GnomAD3 genomes

AF:

0.00791

AC:

1162

AN:

146896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00216

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.00914

Gnomad EAS

AF:

0.000415

Gnomad SAS

AF:

0.00609

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.0323

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.0133

GnomAD2 exomes

AF:

0.00571

AC:

183

AN:

32074

AF XY:

0.00635

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00589

Gnomad ASJ exome

AF:

0.00568

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.00857

Gnomad OTH exome

AF:

0.00954

GnomAD4 exome

AF:

0.00737

AC:

7854

AN:

1065024

Hom.:

Cov.:

AF XY:

0.00747

AC XY:

3811

AN XY:

510288

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00206

AC:

AN:

20924

American (AMR)

AF:

0.00490

AC:

AN:

11424

Ashkenazi Jewish (ASJ)

AF:

0.00913

AC:

121

AN:

13260

East Asian (EAS)

AF:

0.000810

AC:

AN:

19748

South Asian (SAS)

AF:

0.00690

AC:

179

AN:

25952

European-Finnish (FIN)

AF:

0.00313

AC:

AN:

31596

Middle Eastern (MID)

AF:

0.0273

AC:

AN:

2712

European-Non Finnish (NFE)

AF:

0.00773

AC:

6948

AN:

899140

Other (OTH)

AF:

0.00790

AC:

318

AN:

40268

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.369

Heterozygous variant carriers

375

750

1126

1501

1876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.00792

AC:

1164

AN:

147004

Hom.:

Cov.:

AF XY:

0.00794

AC XY:

568

AN XY:

71544

show subpopulations

African (AFR)

AF:

0.00215

AC:

AN:

40424

American (AMR)

AF:

0.0167

AC:

248

AN:

14886

Ashkenazi Jewish (ASJ)

AF:

0.00914

AC:

AN:

3390

East Asian (EAS)

AF:

0.000624

AC:

AN:

4808

South Asian (SAS)

AF:

0.00630

AC:

AN:

4760

European-Finnish (FIN)

AF:

0.00263

AC:

AN:

9136

Middle Eastern (MID)

AF:

0.0350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0104

AC:

688

AN:

66358

Other (OTH)

AF:

0.0132

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

104

157

209

261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00464

Hom.:

ClinVar

ClinVar submissions

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

0.82

Mutation Taster

=81/19

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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