Variant 6-16327675-CTGA-CTGATGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001128164.2(ATXN1):c.633_635dupTCA(p.His211dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000251 in 119,626 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: 𝑓 0.000025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATXN1
NM_001128164.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN1	NM_001128164.2 linkuse as main transcript	c.633_635dupTCA	p.His211dup	disruptive_inframe_insertion	7/8	ENST00000436367.6	NP_001121636.1	P54253-1Q96FF1
ATXN1	NM_000332.4 linkuse as main transcript	c.633_635dupTCA	p.His211dup	disruptive_inframe_insertion	8/9		NP_000323.2	P54253-1Q96FF1
ATXN1	NM_001357857.2 linkuse as main transcript	c.46_48dupTCA		3_prime_UTR_variant	8/9		NP_001344786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATXN1	ENST00000436367.6 linkuse as main transcript	c.633_635dupTCA	p.His211dup	disruptive_inframe_insertion	7/8	1	NM_001128164.2	ENSP00000416360.1	P54253-1
ATXN1	ENST00000244769.8 linkuse as main transcript	c.633_635dupTCA	p.His211dup	disruptive_inframe_insertion	8/9	1		ENSP00000244769.3	P54253-1
ATXN1	ENST00000642969.1 linkuse as main transcript	c.46_48dupTCA		downstream_gene_variant				ENSP00000493530.1	A0A2R8YCF3

Frequencies

GnomAD3 genomes

AF:

0.0000251

AC:

AN:

119626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000487

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000258

AC:

AN:

1395994

Hom.:

Cov.:

AF XY:

0.0000245

AC XY:

AN XY:

694042

show subpopulations

Gnomad4 AFR exome

AF:

0.0000375

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000395

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000296

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

AF:

0.0000251

AC:

AN:

119626

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

58090

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000487

Gnomad4 OTH

AF:

0.00

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