3-63912684-G-GGCAGCAGCAGCA

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_001377405.1(ATXN7):c.107_118dup(p.Gln36_Gln39dup) variant causes a 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. 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 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.10

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 2653938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 460 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN7	NM_001377405.1	c.107_118dup	p.Gln36_Gln39dup	inframe_insertion	3/13	ENST00000674280.1
ATXN7	NM_000333.4	c.107_118dup	p.Gln36_Gln39dup	inframe_insertion	3/13
ATXN7	NM_001177387.1	c.107_118dup	p.Gln36_Gln39dup	inframe_insertion	2/13
ATXN7	NM_001377406.1	c.107_118dup	p.Gln36_Gln39dup	inframe_insertion	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN7	ENST00000674280.1	c.107_118dup	p.Gln36_Gln39dup	inframe_insertion	3/13		NM_001377405.1	P2

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 460 AN: 144612 Hom.: 2 Cov.: 23

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

GnomAD3 exomes AF: 0.00232 AC: 24 AN: 10356 Hom.: 0 AF XY: 0.00198 AC XY: 11 AN XY: 5542

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 SAS exome AF: 0.00195

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.: 11 Cov.: 26 AF XY: 0.00360 AC XY: 1608 AN XY: 446544

Gnomad4 AFR exome AF: 0.00237

Gnomad4 AMR exome AF: 0.00341

Gnomad4 ASJ exome AF: 0.00167

Gnomad4 EAS exome AF: 0.00125

Gnomad4 SAS exome AF: 0.00944

Gnomad4 FIN exome AF: 0.00339

Gnomad4 NFE exome AF: 0.00349

Gnomad4 OTH exome AF: 0.00381

GnomAD4 genome AF: 0.00319 AC: 461 AN: 144714 Hom.: 2 Cov.: 23 AF XY: 0.00345 AC XY: 243 AN XY: 70410

Gnomad4 AFR AF: 0.00218

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.000593

Gnomad4 EAS AF: 0.00168

Gnomad4 SAS AF: 0.00892

Gnomad4 FIN AF: 0.00153

Gnomad4 NFE AF: 0.00339

Gnomad4 OTH AF: 0.00591

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

ATXN7: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs193922929; hg19: chr3-63898360;