Genetic Variant ATXN10:c.1003+214G>A (chr22-45739053-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_013236.4(ATXN10):c.1003+214G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,158 control chromosomes in the GnomAD database, including 4,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 4124 hom., cov: 32)

Consequence

ATXN10
NM_013236.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.149

Publications

1 publications found

Variant links:

Genes affected

ATXN10 (HGNC:10549): (ataxin 10) This gene encodes a protein that may function in neuron survival, neuron differentiation, and neuritogenesis. These roles may be carried out via activation of the mitogen-activated protein kinase cascade. Expansion of an ATTCT repeat from 9-32 copies to 800-4500 copies in an intronic region of this locus has been associated with spinocerebellar ataxia, type 10. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jul 2016]

ATXN10 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 10
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ATXN10 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=-0.88).

BP6

Variant 22-45739053-G-A is Benign according to our data. Variant chr22-45739053-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257197.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013236.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	NM_013236.4	MANE Select	c.1003+214G>A		intron	N/A	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.811+214G>A		intron	N/A	NP_001161093.1	Q9UBB4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATXN10	ENST00000252934.10	TSL:1 MANE Select	c.1003+214G>A	intron	N/A	ENSP00000252934.4	Q9UBB4-1
ATXN10	ENST00000381061.8	TSL:2	c.811+214G>A	intron	N/A	ENSP00000370449.4	Q9UBB4-2
ATXN10	ENST00000435026.5	TSL:3	c.259+214G>A	intron	N/A	ENSP00000391117.1	B1AHE4

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33209

AN:

152040

Hom.:

4121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.218

AC:

33245

AN:

152158

Hom.:

4124

Cov.:

AF XY:

0.217

AC XY:

16145

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.354

AC:

14684

AN:

41480

American (AMR)

AF:

0.162

AC:

2470

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

537

AN:

3470

East Asian (EAS)

AF:

0.209

AC:

1082

AN:

5188

South Asian (SAS)

AF:

0.150

AC:

723

AN:

4820

European-Finnish (FIN)

AF:

0.180

AC:

1912

AN:

10594

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.165

AC:

11204

AN:

68000

Other (OTH)

AF:

0.190

AC:

402

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1300

2600

3899

5199

6499

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.181

Hom.:

8595

Bravo

AF:

0.223

Asia WGS

AF:

0.174

AC:

605

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.42

(source)

DANN

Benign

0.29

PhyloP100

-0.15

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over