Variant 6-16327684-ATGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-ATGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_001128164.2(ATXN1):c.626_627insGCAGCAGCAGCAGCA(p.Gln204_Gln208dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.019 ( 36 hom., cov: 20)

Exomes 𝑓: 0.014 ( 146 hom. )

Failed GnomAD Quality Control

Consequence

ATXN1
NM_001128164.2 inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.106

Variant links:

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]

ATXN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0189 (2541/134688) while in subpopulation NFE AF= 0.0233 (1504/64538). AF 95% confidence interval is 0.0223. There are 36 homozygotes in gnomad4. There are 1279 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2541 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATXN1	NM_001128164.2 linkuse as main transcript	c.626_627insGCAGCAGCAGCAGCA	p.Gln204_Gln208dup	inframe_insertion	7/8	ENST00000436367.6	NP_001121636.1
ATXN1	NM_000332.4 linkuse as main transcript	c.626_627insGCAGCAGCAGCAGCA	p.Gln204_Gln208dup	inframe_insertion	8/9		NP_000323.2
ATXN1	NM_001357857.2 linkuse as main transcript	c.39_40insGCAGCAGCAGCAGCA		3_prime_UTR_variant	8/9		NP_001344786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN1	ENST00000436367.6 linkuse as main transcript	c.626_627insGCAGCAGCAGCAGCA	p.Gln204_Gln208dup	inframe_insertion	7/8	1	NM_001128164.2	ENSP00000416360	P1	P54253-1
ATXN1	ENST00000244769.8 linkuse as main transcript	c.626_627insGCAGCAGCAGCAGCA	p.Gln204_Gln208dup	inframe_insertion	8/9	1		ENSP00000244769	P1	P54253-1
ATXN1	ENST00000642969.1 linkuse as main transcript			downstream_gene_variant				ENSP00000493530

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2542

AN:

134590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00579

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.0119

Gnomad EAS

AF:

0.000247

Gnomad SAS

AF:

0.00960

Gnomad FIN

AF:

0.0352

Gnomad MID

AF:

0.0109

Gnomad NFE

AF:

0.0233

Gnomad OTH

AF:

0.0132

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0138

AC:

18289

AN:

1323104

Hom.:

146

Cov.:

AF XY:

0.0135

AC XY:

8902

AN XY:

657492

show subpopulations

Gnomad4 AFR exome

AF:

0.00842

Gnomad4 AMR exome

AF:

0.00448

Gnomad4 ASJ exome

AF:

0.00765

Gnomad4 EAS exome

AF:

0.000784

Gnomad4 SAS exome

AF:

0.00938

Gnomad4 FIN exome

AF:

0.0333

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0138

GnomAD4 genome

AF:

0.0189

AC:

2541

AN:

134688

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

1279

AN XY:

65476

show subpopulations

Gnomad4 AFR

AF:

0.0137

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.0119

Gnomad4 EAS

AF:

0.000248

Gnomad4 SAS

AF:

0.00961

Gnomad4 FIN

AF:

0.0352

Gnomad4 NFE

AF:

0.0233

Gnomad4 OTH

AF:

0.0131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over