6-16327684-ATGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-ATGCTGCTGCTGCTGCTGCTGCTGC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001128164.2(ATXN1):c.621_626del(p.Gln207_Gln208del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0033 (4 hom., cov: 20)
  • Exomes 𝑓: 0.00045 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATXN1 NM_001128164.2 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

Genes affected

ATXN1 (HGNC:10548): (ataxin 1) 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. The function of the ataxins is not known. This locus has been mapped to chromosome 6, and it has been determined that the diseased allele contains 40-83 CAG repeats, compared to 6-39 in the normal allele, and is associated with spinocerebellar ataxia type 1 (SCA1). Alternative splicing results in multiple transcript variants, with one variant encoding multiple distinct proteins, ATXN1 and Alt-ATXN1, due to the use of overlapping alternate reading frames. [provided by RefSeq, Nov 2017]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 6-16327684-ATGCTGC-A is Benign according to our data. Variant chr6-16327684-ATGCTGC-A is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 434 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN1	NM_001128164.2	c.621_626del	p.Gln207_Gln208del	inframe_deletion	7/8	ENST00000436367.6
ATXN1	NM_000332.4	c.621_626del	p.Gln207_Gln208del	inframe_deletion	8/9
ATXN1	NM_001357857.2	c.*34_*39del		3_prime_UTR_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN1	ENST00000436367.6	c.621_626del	p.Gln207_Gln208del	inframe_deletion	7/8	1	NM_001128164.2	P1
ATXN1	ENST00000244769.8	c.621_626del	p.Gln207_Gln208del	inframe_deletion	8/9	1		P1
ATXN1	ENST00000642969.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00322 AC: 434 AN: 134614 Hom.: 4 Cov.: 20

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00128

Gnomad ASJ AF: 0.000305

Gnomad EAS AF: 0.00148

Gnomad SAS AF: 0.00152

Gnomad FIN AF: 0.000204

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000465

Gnomad OTH AF: 0.00110

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000445 AC: 596 AN: 1338174 Hom.: 2 AF XY: 0.000435 AC XY: 289 AN XY: 664824

Gnomad4 AFR exome AF: 0.00924

Gnomad4 AMR exome AF: 0.000678

Gnomad4 ASJ exome AF: 0.0000402

Gnomad4 EAS exome AF: 0.000667

Gnomad4 SAS exome AF: 0.00137

Gnomad4 FIN exome AF: 0.000199

Gnomad4 NFE exome AF: 0.000128

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.00326 AC: 439 AN: 134710 Hom.: 4 Cov.: 20 AF XY: 0.00311 AC XY: 204 AN XY: 65498

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.00128

Gnomad4 ASJ AF: 0.000305

Gnomad4 EAS AF: 0.00149

Gnomad4 SAS AF: 0.00152

Gnomad4 FIN AF: 0.000204

Gnomad4 NFE AF: 0.000465

Gnomad4 OTH AF: 0.00109

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: rs193922926; hg19: chr6-16327915;