6-16327684-ATGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-ATGCTGC

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_001128164.2(ATXN1):c.603_626delGCAGCAGCAGCAGCAGCAGCAGCA(p.Gln201_Gln208del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,474,188 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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 0.000022 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ATXN1
NM_001128164.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.123

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, Orphanet, Labcorp Genetics (formerly Invitae)

ATXN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001128164.2

BS2

High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ATXN1	NM_001128164.2 link	c.603_626delGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln201_Gln208del	disruptive_inframe_deletion	Exon 7 of 8	ENST00000436367.6	NP_001121636.1
ATXN1	NM_000332.4 link	c.603_626delGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln201_Gln208del	disruptive_inframe_deletion	Exon 8 of 9		NP_000323.2
ATXN1	NM_001357857.2 link	c.16_39delGCAGCAGCAGCAGCAGCAGCAGCA		3_prime_UTR_variant	Exon 8 of 9		NP_001344786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ATXN1	ENST00000436367.6 link	c.603_626delGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln201_Gln208del	disruptive_inframe_deletion	Exon 7 of 8	1	NM_001128164.2	ENSP00000416360.1
ATXN1	ENST00000244769.8 link	c.603_626delGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln201_Gln208del	disruptive_inframe_deletion	Exon 8 of 9	1		ENSP00000244769.3
ATXN1	ENST00000642969.1 link	c.16_39delGCAGCAGCAGCAGCAGCAGCAGCA		downstream_gene_variant				ENSP00000493530.1

Frequencies

GnomAD3 genomes

AF:

0.0000223

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:

0.000247

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000102

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000155

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1339446

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

665478

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26546

American (AMR)

AF:

0.0000563

AC:

AN:

35508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24870

East Asian (EAS)

AF:

0.00

AC:

AN:

30604

South Asian (SAS)

AF:

0.0000134

AC:

AN:

74462

European-Finnish (FIN)

AF:

0.000174

AC:

AN:

40210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4600

European-Non Finnish (NFE)

AF:

0.0000115

AC:

AN:

1047580

Other (OTH)

AF:

0.0000363

AC:

AN:

55066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.0000223

AC:

AN:

134742

Hom.:

Cov.:

AF XY:

0.0000458

AC XY:

AN XY:

65508

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:

32836

American (AMR)

AF:

0.00

AC:

AN:

13314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3278

East Asian (EAS)

AF:

0.000248

AC:

AN:

4028

South Asian (SAS)

AF:

0.00

AC:

AN:

3956

European-Finnish (FIN)

AF:

0.000102

AC:

AN:

9816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

64558

Other (OTH)

AF:

0.00

AC:

AN:

1834

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0706630), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.12

Mutation Taster

=187/13

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over