3-63912684-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCA

Position:

• chr3-63912684-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3 BP6 BS1 BS2

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. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.016 (34 hom., cov: 23)
  • Exomes 𝑓: 0.0086 (63 hom.)
• Consequence: ATXN7 NM_001377405.1 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.84

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 -10 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001377405.1
• BP6: Variant 3-63912684-GGCAGCAGCA-G is Benign according to our data. Variant chr3-63912684-GGCAGCAGCA-G is described in Lovd as [Benign].
• 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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2313 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN7	NM_001377405.1	c.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	3/13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1	c.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	2/13		NP_001170858.1
ATXN7	NM_000333.4	c.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	3/13		NP_000324.1
ATXN7	NM_001377406.1	c.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	2/12		NP_001364335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7	ENST00000674280.1	c.110_118delAGCAGCAGC	p.Gln37_Gln39del	disruptive_inframe_deletion	3/13		NM_001377405.1	ENSP00000501377.1

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2313 AN: 144598 Hom.: 34 Cov.: 23

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

GnomAD3 exomes AF: 0.0105 AC: 109 AN: 10356 Hom.: 1 AF XY: 0.00848 AC XY: 47 AN XY: 5542

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 SAS 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.: 63 AF XY: 0.00855 AC XY: 3819 AN XY: 446504

Gnomad4 AFR exome AF: 0.0319

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.0466

Gnomad4 EAS exome AF: 0.0310

Gnomad4 SAS exome AF: 0.00435

Gnomad4 FIN exome AF: 0.0165

Gnomad4 NFE exome AF: 0.00737

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.0160 AC: 2313 AN: 144700 Hom.: 34 Cov.: 23 AF XY: 0.0156 AC XY: 1096 AN XY: 70400

Gnomad4 AFR AF: 0.0298

Gnomad4 AMR AF: 0.00755

Gnomad4 ASJ AF: 0.0560

Gnomad4 EAS AF: 0.0229

Gnomad4 SAS AF: 0.00404

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.00787

Gnomad4 OTH AF: 0.0153

ClinVar

Not reported in ClinVar

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;