6-16327684-ATGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-ATGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001128164.2(ATXN1):c.597_626dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA(p.Gln199_Gln208dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000030 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000014 ( 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: 0.106

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 1
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ATXN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001128164.2

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128164.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN1	NM_001128164.2	MANE Select	c.597_626dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln199_Gln208dup	disruptive_inframe_insertion	Exon 7 of 8	NP_001121636.1	P54253-1
ATXN1	NM_000332.4		c.597_626dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln199_Gln208dup	disruptive_inframe_insertion	Exon 8 of 9	NP_000323.2	P54253-1
ATXN1	NM_001357857.2		c.10_39dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA		3_prime_UTR	Exon 8 of 9	NP_001344786.1	A0A2R8YCF3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN1	ENST00000436367.6	TSL:1 MANE Select	c.597_626dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln199_Gln208dup	disruptive_inframe_insertion	Exon 7 of 8	ENSP00000416360.1	P54253-1
ATXN1	ENST00000244769.8	TSL:1	c.597_626dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln199_Gln208dup	disruptive_inframe_insertion	Exon 8 of 9	ENSP00000244769.3	P54253-1
ATXN1	ENST00000642969.1		c.10_39dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA		downstream_gene	N/A	ENSP00000493530.1	A0A2R8YCF3

Frequencies

GnomAD3 genomes

AF:

0.0000297

AC:

AN:

134644

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:

0.0000465

Gnomad OTH

AF:

0.000551

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000142

AC:

AN:

1339434

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

665464

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

26546

American (AMR)

AF:

0.00

AC:

AN:

35506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24870

East Asian (EAS)

AF:

0.00

AC:

AN:

30604

South Asian (SAS)

AF:

0.0000672

AC:

AN:

74456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40210

Middle Eastern (MID)

AF:

0.000217

AC:

AN:

4600

European-Non Finnish (NFE)

AF:

0.0000105

AC:

AN:

1047580

Other (OTH)

AF:

0.0000363

AC:

AN:

55062

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000143108), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.343

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000297

AC:

AN:

134644

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

65412

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32724

American (AMR)

AF:

0.00

AC:

AN:

13302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3278

East Asian (EAS)

AF:

0.00

AC:

AN:

4042

South Asian (SAS)

AF:

0.00

AC:

AN:

3958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.0000465

AC:

AN:

64568

Other (OTH)

AF:

0.000551

AC:

AN:

1816

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.11

Mutation Taster

=91/9

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over