3-63912684-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCA

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BS1BS2

The NM_001377405.1(ATXN7):c.110_118delAGCAGCAGC(p.Gln37_Gln39del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00962 in 1,087,000 control chromosomes in the GnomAD database, including 97 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.016 ( 34 hom., cov: 23)

Exomes 𝑓: 0.0086 ( 63 hom. )

Consequence

ATXN7
NM_001377405.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.84

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 -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001377405.1

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.016 (2313/144700) while in subpopulation AFR AF = 0.0298 (1192/39986). AF 95% confidence interval is 0.0284. There are 34 homozygotes in GnomAd4. There are 1096 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High AC in GnomAd4 at 2313 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.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	Exon 3 of 13	NP_001364334.1	O15265-1
ATXN7	NM_001177387.1		c.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	Exon 2 of 13	NP_001170858.1	O15265-2
ATXN7	NM_000333.4		c.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	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.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	Exon 3 of 13	ENSP00000501377.1	O15265-1
ATXN7	ENST00000295900.10	TSL:1	c.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	Exon 3 of 13	ENSP00000295900.6	O15265-1
ATXN7	ENST00000522345.2	TSL:2	c.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	Exon 1 of 12	ENSP00000428067.2	O15265-2

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2313

AN:

144598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0299

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00756

Gnomad ASJ

AF:

0.0560

Gnomad EAS

AF:

0.0226

Gnomad SAS

AF:

0.00446

Gnomad FIN

AF:

0.0173

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00787

Gnomad OTH

AF:

0.0154

GnomAD2 exomes

AF:

0.0105

AC:

109

AN:

10356

AF XY:

0.00848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00872

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0183

Gnomad NFE exome

AF:

0.00444

Gnomad OTH exome

AF:

0.00500

GnomAD4 exome

AF:

0.00864

AC:

8142

AN:

942300

Hom.:

AF XY:

0.00855

AC XY:

3819

AN XY:

446504

show subpopulations

African (AFR)

AF:

0.0319

AC:

565

AN:

17712

American (AMR)

AF:

0.00208

AC:

AN:

5282

Ashkenazi Jewish (ASJ)

AF:

0.0466

AC:

390

AN:

8378

East Asian (EAS)

AF:

0.0310

AC:

297

AN:

9584

South Asian (SAS)

AF:

0.00435

AC:

AN:

20022

European-Finnish (FIN)

AF:

0.0165

AC:

311

AN:

18844

Middle Eastern (MID)

AF:

0.00620

AC:

AN:

2096

European-Non Finnish (NFE)

AF:

0.00737

AC:

6100

AN:

827288

Other (OTH)

AF:

0.0111

AC:

368

AN:

33094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

400

800

1201

1601

2001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.0160

AC:

2313

AN:

144700

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1096

AN XY:

70400

show subpopulations

African (AFR)

AF:

0.0298

AC:

1192

AN:

39986

American (AMR)

AF:

0.00755

AC:

111

AN:

14702

Ashkenazi Jewish (ASJ)

AF:

0.0560

AC:

189

AN:

3374

East Asian (EAS)

AF:

0.0229

AC:

109

AN:

4764

South Asian (SAS)

AF:

0.00404

AC:

AN:

4708

European-Finnish (FIN)

AF:

0.0173

AC:

147

AN:

8508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00787

AC:

515

AN:

65440

Other (OTH)

AF:

0.0153

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

104

208

311

415

519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00193

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.8

Mutation Taster

=195/5

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