3-63912684-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCA

Variant names:

• chr3-63912684-GGCAGCA-G
• rs193922929
• NM_001377405.1:c.113_118delAGCAGC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001377405.1(ATXN7):​c.113_118delAGCAGC​(p.Gln38_Gln39del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00125 in 1,087,052 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0012 (0 hom.)
• Consequence: ATXN7 NM_001377405.1 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.84
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001377405.1
• BS2: High AC in GnomAd4 at 218 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN7	NM_001377405.1	MANE Select	c.113_118delAGCAGC	p.Gln38_Gln39del	disruptive_inframe_deletion	Exon 3 of 13	NP_001364334.1	O15265-1
	ATXN7	NM_001177387.1		c.113_118delAGCAGC	p.Gln38_Gln39del	disruptive_inframe_deletion	Exon 2 of 13	NP_001170858.1	O15265-2
	ATXN7	NM_000333.4		c.113_118delAGCAGC	p.Gln38_Gln39del	disruptive_inframe_deletion	Exon 3 of 13	NP_000324.1	O15265-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN7	ENST00000674280.1	MANE Select	c.113_118delAGCAGC	p.Gln38_Gln39del	disruptive_inframe_deletion	Exon 3 of 13	ENSP00000501377.1	O15265-1
	ATXN7	ENST00000295900.10	TSL:1	c.113_118delAGCAGC	p.Gln38_Gln39del	disruptive_inframe_deletion	Exon 3 of 13	ENSP00000295900.6	O15265-1
	ATXN7	ENST00000522345.2	TSL:2	c.113_118delAGCAGC	p.Gln38_Gln39del	disruptive_inframe_deletion	Exon 1 of 12	ENSP00000428067.2	O15265-2

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 217 AN: 144616 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00361

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000953

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000871

Gnomad OTH AF: 0.000996

GnomAD4 exome AF: 0.00121 AC: 1140 AN: 942334 Hom.: 0 AF XY: 0.00121 AC XY: 539 AN XY: 446524

African (AFR) AF: 0.00344 AC: 61 AN: 17716

American (AMR) AF: 0.000948 AC: 5 AN: 5274

Ashkenazi Jewish (ASJ) AF: 0.000119 AC: 1 AN: 8398

East Asian (EAS) AF: 0.00 AC: 0 AN: 9608

South Asian (SAS) AF: 0.000150 AC: 3 AN: 20014

European-Finnish (FIN) AF: 0.000637 AC: 12 AN: 18846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2094

European-Non Finnish (NFE) AF: 0.00123 AC: 1019 AN: 827282

Other (OTH) AF: 0.00118 AC: 39 AN: 33102

GnomAD4 genome AF: 0.00151 AC: 218 AN: 144718 Hom.: 0 Cov.: 23 AF XY: 0.00126 AC XY: 89 AN XY: 70412

African (AFR) AF: 0.00360 AC: 144 AN: 39998

American (AMR) AF: 0.000952 AC: 14 AN: 14702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3374

East Asian (EAS) AF: 0.00 AC: 0 AN: 4766

South Asian (SAS) AF: 0.00 AC: 0 AN: 4708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000886 AC: 58 AN: 65440

Other (OTH) AF: 0.000985 AC: 2 AN: 2030

Alfa AF: 0.00 Hom.: 39

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.8
Mutation Taster		=165/35	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs193922929; hg19: chr3-63898360;