3-63912714-A-AGCAGCAGCAGCCGCAGCAGCC

Variant names:

• chr3-63912714-A-AGCAGCAGCAGCCGCAGCAGCC
• NM_001377405.1:c.118_119insAGCAGCAGCCGCAGCAGCCGC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The NM_001377405.1(ATXN7):​c.118_119insAGCAGCAGCCGCAGCAGCCGC​(p.Gln39_Pro40insGlnGlnGlnProGlnGlnPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000938 in 1,065,664 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: not found (cov: 31)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: ATXN7 NM_001377405.1 disruptive_inframe_insertion
• 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_001377405.1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7	NM_001377405.1	c.118_119insAGCAGCAGCCGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnProGlnGlnPro	disruptive_inframe_insertion	Exon 3 of 13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1	c.118_119insAGCAGCAGCCGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnProGlnGlnPro	disruptive_inframe_insertion	Exon 2 of 13		NP_001170858.1
ATXN7	NM_000333.4	c.118_119insAGCAGCAGCCGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnProGlnGlnPro	disruptive_inframe_insertion	Exon 3 of 13		NP_000324.1
ATXN7	NM_001377406.1	c.118_119insAGCAGCAGCCGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnProGlnGlnPro	disruptive_inframe_insertion	Exon 2 of 12		NP_001364335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN7	ENST00000674280.1	c.118_119insAGCAGCAGCCGCAGCAGCCGC	p.Gln39_Pro40insGlnGlnGlnProGlnGlnPro	disruptive_inframe_insertion	Exon 3 of 13		NM_001377405.1	ENSP00000501377.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.38e-7 AC: 1 AN: 1065664 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 510618

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000248

GnomAD4 genome Cov.: 31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-63898390;