Variant chr6-16327684-A-ATGCTGCTGCTGCTGCTGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001128164.2(ATXN1):c.626_627insGCAGCAGCAGCAGCAGCA(p.Gln203_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 0.0034 ( 4 hom., cov: 20)

Exomes 𝑓: 0.0012 ( 4 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 458 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ATXN1	NM_001128164.2 linkuse as main transcript	c.626_627insGCAGCAGCAGCAGCAGCA	p.Gln203_Gln208dup	inframe_insertion	7/8	ENST00000436367.6
ATXN1	NM_000332.4 linkuse as main transcript	c.626_627insGCAGCAGCAGCAGCAGCA	p.Gln203_Gln208dup	inframe_insertion	8/9
ATXN1	NM_001357857.2 linkuse as main transcript	c.39_40insGCAGCAGCAGCAGCAGCA		3_prime_UTR_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN1	ENST00000436367.6 linkuse as main transcript	c.626_627insGCAGCAGCAGCAGCAGCA	p.Gln203_Gln208dup	inframe_insertion	7/8	1	NM_001128164.2	P1	P54253-1
ATXN1	ENST00000244769.8 linkuse as main transcript	c.626_627insGCAGCAGCAGCAGCAGCA	p.Gln203_Gln208dup	inframe_insertion	8/9	1		P1	P54253-1
ATXN1	ENST00000642969.1 linkuse as main transcript			downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00340

AC:

458

AN:

134632

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00807

Gnomad AMI

AF:

0.0266

Gnomad AMR

AF:

0.000601

Gnomad ASJ

AF:

0.00427

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00328

Gnomad FIN

AF:

0.000509

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00195

Gnomad OTH

AF:

0.00275

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00120

AC:

1599

AN:

1337988

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

848

AN XY:

664820

show subpopulations

Gnomad4 AFR exome

AF:

0.00601

Gnomad4 AMR exome

AF:

0.000423

Gnomad4 ASJ exome

AF:

0.00242

Gnomad4 EAS exome

AF:

0.0000980

Gnomad4 SAS exome

AF:

0.00290

Gnomad4 FIN exome

AF:

0.000597

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.00340

AC:

458

AN:

134730

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

225

AN XY:

65502

show subpopulations

Gnomad4 AFR

AF:

0.00804

Gnomad4 AMR

AF:

0.000601

Gnomad4 ASJ

AF:

0.00427

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00329

Gnomad4 FIN

AF:

0.000509

Gnomad4 NFE

AF:

0.00195

Gnomad4 OTH

AF:

0.00273

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