NM_001128164.2:c.1212A>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.1212A>G(p.Glu404Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,613,450 control chromosomes in the GnomAD database, including 49,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.29 ( 7123 hom., cov: 32)

Exomes 𝑓: 0.23 ( 42722 hom. )

Consequence

ATXN1
NM_001128164.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0320

Publications

15 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 6-16327099-T-C is Benign according to our data. Variant chr6-16327099-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 128498.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.032 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN1	NM_001128164.2 link	c.1212A>G	p.Glu404Glu	synonymous_variant	Exon 7 of 8	ENST00000436367.6	NP_001121636.1	P54253-1Q96FF1
ATXN1	NM_000332.4 link	c.1212A>G	p.Glu404Glu	synonymous_variant	Exon 8 of 9		NP_000323.2	P54253-1Q96FF1
ATXN1	NM_001357857.2 link	c.*625A>G		3_prime_UTR_variant	Exon 8 of 9		NP_001344786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN1	ENST00000436367.6 link	c.1212A>G	p.Glu404Glu	synonymous_variant	Exon 7 of 8	1	NM_001128164.2	ENSP00000416360.1		P54253-1
ATXN1	ENST00000244769.8 link	c.1212A>G	p.Glu404Glu	synonymous_variant	Exon 8 of 9	1		ENSP00000244769.3		P54253-1

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43462

AN:

151938

Hom.:

7104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.0802

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.286

GnomAD2 exomes

AF:

0.264

AC:

66340

AN:

250906

AF XY:

0.264

show subpopulations

Gnomad AFR exome

AF:

0.445

Gnomad AMR exome

AF:

0.222

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.231

AC:

337942

AN:

1461394

Hom.:

42722

Cov.:

AF XY:

0.235

AC XY:

170535

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.449

AC:

15047

AN:

33480

American (AMR)

AF:

0.226

AC:

10112

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

5436

AN:

26136

East Asian (EAS)

AF:

0.480

AC:

19040

AN:

39700

South Asian (SAS)

AF:

0.362

AC:

31207

AN:

86258

European-Finnish (FIN)

AF:

0.185

AC:

9775

AN:

52934

Middle Eastern (MID)

AF:

0.239

AC:

1378

AN:

5768

European-Non Finnish (NFE)

AF:

0.208

AC:

230808

AN:

1112002

Other (OTH)

AF:

0.251

AC:

15139

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

18849

37699

56548

75398

94247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8438

16876

25314

33752

42190

<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:

0.286

AC:

43517

AN:

152056

Hom.:

7123

Cov.:

AF XY:

0.287

AC XY:

21336

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.436

AC:

18082

AN:

41446

American (AMR)

AF:

0.249

AC:

3811

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

729

AN:

3468

East Asian (EAS)

AF:

0.479

AC:

2461

AN:

5140

South Asian (SAS)

AF:

0.372

AC:

1793

AN:

4824

European-Finnish (FIN)

AF:

0.173

AC:

1833

AN:

10604

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

14024

AN:

67964

Other (OTH)

AF:

0.295

AC:

623

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1556

3111

4667

6222

7778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.248

Hom.:

4955

Bravo

AF:

0.298

Asia WGS

AF:

0.466

AC:

1616

AN:

3478

EpiCase

AF:

0.205

EpiControl

AF:

0.211

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.9

(source)

DANN

Benign

0.44

PhyloP100

0.032

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over