3-63912684-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCA

Variant names:

• chr3-63912684-GGCAGCAGCAGCA-G
• rs193922929
• NM_001377405.1:c.107_118delAGCAGCAGCAGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3 BP6 BS2

The NM_001377405.1(ATXN7):​c.107_118delAGCAGCAGCAGC​(p.Gln36_Gln39del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000167 in 1,087,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00015 (0 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 Likely_benign. Variant got -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001377405.1
• BP6: Variant 3-63912684-GGCAGCAGCAGCA-G is Benign according to our data. Variant chr3-63912684-GGCAGCAGCAGCA-G is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7	NM_001377405.1	c.107_118delAGCAGCAGCAGC	p.Gln36_Gln39del	disruptive_inframe_deletion	Exon 3 of 13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1	c.107_118delAGCAGCAGCAGC	p.Gln36_Gln39del	disruptive_inframe_deletion	Exon 2 of 13		NP_001170858.1
ATXN7	NM_000333.4	c.107_118delAGCAGCAGCAGC	p.Gln36_Gln39del	disruptive_inframe_deletion	Exon 3 of 13		NP_000324.1
ATXN7	NM_001377406.1	c.107_118delAGCAGCAGCAGC	p.Gln36_Gln39del	disruptive_inframe_deletion	Exon 2 of 12		NP_001364335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN7	ENST00000674280.1	c.107_118delAGCAGCAGCAGC	p.Gln36_Gln39del	disruptive_inframe_deletion	Exon 3 of 13		NM_001377405.1	ENSP00000501377.1

Frequencies

GnomAD3 genomes AF: 0.000242 AC: 35 AN: 144616 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000426

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000204

Gnomad ASJ AF: 0.000889

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000153

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000155 AC: 146 AN: 942420 Hom.: 0 AF XY: 0.000170 AC XY: 76 AN XY: 446580

Gnomad4 AFR exome AF: 0.000565

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000238

Gnomad4 EAS exome AF: 0.000104

Gnomad4 SAS exome AF: 0.000450

Gnomad4 FIN exome AF: 0.0000530

Gnomad4 NFE exome AF: 0.000140

Gnomad4 OTH exome AF: 0.000211

GnomAD4 genome AF: 0.000242 AC: 35 AN: 144616 Hom.: 0 Cov.: 23 AF XY: 0.000256 AC XY: 18 AN XY: 70298

Gnomad4 AFR AF: 0.000426

Gnomad4 AMR AF: 0.000204

Gnomad4 ASJ AF: 0.000889

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000425

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000153

Gnomad4 OTH AF: 0.00

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;