6-16327384-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001128164.2(ATXN1):c.927T>C(p.Ala309Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 1,613,212 control chromosomes in the GnomAD database, including 399,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. A309A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.73 ( 40517 hom., cov: 32)

Exomes 𝑓: 0.70 ( 358933 hom. )

Consequence

ATXN1
NM_001128164.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.46

Publications

21 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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-16327384-A-G is Benign according to our data. Variant chr6-16327384-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 128505.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

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
ATXN1	NM_001128164.2	MANE Select	c.927T>C	p.Ala309Ala	synonymous	Exon 7 of 8	NP_001121636.1
ATXN1	NM_000332.4		c.927T>C	p.Ala309Ala	synonymous	Exon 8 of 9	NP_000323.2
ATXN1	NM_001357857.2		c.*340T>C		3_prime_UTR	Exon 8 of 9	NP_001344786.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN1	ENST00000436367.6	TSL:1 MANE Select	c.927T>C	p.Ala309Ala	synonymous	Exon 7 of 8	ENSP00000416360.1
	ATXN1	ENST00000244769.8	TSL:1	c.927T>C	p.Ala309Ala	synonymous	Exon 8 of 9	ENSP00000244769.3

Frequencies

GnomAD3 genomes

AF:

0.728

AC:

110570

AN:

151886

Hom.:

40474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.794

Gnomad AMI

AF:

0.737

Gnomad AMR

AF:

0.771

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.863

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.674

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.679

Gnomad OTH

AF:

0.725

GnomAD2 exomes

AF:

0.731

AC:

183269

AN:

250822

AF XY:

0.726

show subpopulations

Gnomad AFR exome

AF:

0.794

Gnomad AMR exome

AF:

0.829

Gnomad ASJ exome

AF:

0.647

Gnomad EAS exome

AF:

0.860

Gnomad FIN exome

AF:

0.669

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.703

GnomAD4 exome

AF:

0.699

AC:

1021351

AN:

1461208

Hom.:

358933

Cov.:

117

AF XY:

0.700

AC XY:

508753

AN XY:

726934

show subpopulations

African (AFR)

AF:

0.793

AC:

26538

AN:

33480

American (AMR)

AF:

0.822

AC:

36761

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

16888

AN:

26126

East Asian (EAS)

AF:

0.876

AC:

34753

AN:

39694

South Asian (SAS)

AF:

0.769

AC:

66290

AN:

86256

European-Finnish (FIN)

AF:

0.669

AC:

35350

AN:

52836

Middle Eastern (MID)

AF:

0.623

AC:

3592

AN:

5768

European-Non Finnish (NFE)

AF:

0.683

AC:

759198

AN:

1111946

Other (OTH)

AF:

0.695

AC:

41981

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

23581

47162

70744

94325

117906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19584

39168

58752

78336

97920

<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:

0.728

AC:

110662

AN:

152004

Hom.:

40517

Cov.:

AF XY:

0.731

AC XY:

54280

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.793

AC:

32922

AN:

41496

American (AMR)

AF:

0.771

AC:

11783

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.630

AC:

2182

AN:

3464

East Asian (EAS)

AF:

0.862

AC:

4439

AN:

5148

South Asian (SAS)

AF:

0.767

AC:

3699

AN:

4822

European-Finnish (FIN)

AF:

0.674

AC:

7115

AN:

10560

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.679

AC:

46126

AN:

67928

Other (OTH)

AF:

0.729

AC:

1535

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1555

3110

4666

6221

7776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.697

Hom.:

30410

Bravo

AF:

0.738

EpiCase

AF:

0.673

EpiControl

AF:

0.667

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.8

(source)

DANN

Benign

0.27

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over