rs1553686135

Variant names:

• chr3-63912714-AGCC-A
• NM_001377405.1:c.123_125delGCC

Your query was ambiguous. Multiple possible variants found:

• chr3-63912714-AGCC-A
• chr3-63912714-AGCC-AGCCGCC
• chr3-63912714-AGCC-AGCCGCCGCC
• chr3-63912714-AGCC-AGCCGCCGCCGCC
• chr3-63912714-AGCC-AGCCGCCGCCGCCGCC

Variant summary

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

The NM_001377405.1(ATXN7):​c.123_125delGCC​(p.Pro42del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000563 in 1,065,656 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: ATXN7 NM_001377405.1 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825

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 3-63912714-AGCC-A is Benign according to our data. Variant chr3-63912714-AGCC-A is described in Lovd as [Benign].
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7	NM_001377405.1	c.123_125delGCC	p.Pro42del	disruptive_inframe_deletion	Exon 3 of 13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1	c.123_125delGCC	p.Pro42del	disruptive_inframe_deletion	Exon 2 of 13		NP_001170858.1
ATXN7	NM_000333.4	c.123_125delGCC	p.Pro42del	disruptive_inframe_deletion	Exon 3 of 13		NP_000324.1
ATXN7	NM_001377406.1	c.123_125delGCC	p.Pro42del	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.123_125delGCC	p.Pro42del	disruptive_inframe_deletion	Exon 3 of 13		NM_001377405.1	ENSP00000501377.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000563 AC: 6 AN: 1065656 Hom.: 0 AF XY: 0.00000392 AC XY: 2 AN XY: 510614

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000385

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000333

Gnomad4 OTH exome AF: 0.0000496

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-63898390;