22-45718518-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013236.4(ATXN10):​c.728+25G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,594,808 control chromosomes in the GnomAD database, including 100,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14627 hom., cov: 31)
Exomes 𝑓: 0.34 ( 86077 hom. )

Consequence

ATXN10
NM_013236.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.14
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 22-45718518-G-T is Benign according to our data. Variant chr22-45718518-G-T is described in ClinVar as [Benign]. Clinvar id is 1250676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATXN10NM_013236.4 linkc.728+25G>T intron_variant Intron 6 of 11 ENST00000252934.10 NP_037368.1 Q9UBB4-1
ATXN10NM_001167621.2 linkc.536+25G>T intron_variant Intron 5 of 10 NP_001161093.1 Q9UBB4-2
ATXN10XM_047441314.1 linkc.728+25G>T intron_variant Intron 6 of 11 XP_047297270.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATXN10ENST00000252934.10 linkc.728+25G>T intron_variant Intron 6 of 11 1 NM_013236.4 ENSP00000252934.4 Q9UBB4-1

Frequencies

GnomAD3 genomes
AF:
0.414
AC:
62823
AN:
151866
Hom.:
14588
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.644
Gnomad AMI
AF:
0.321
Gnomad AMR
AF:
0.305
Gnomad ASJ
AF:
0.381
Gnomad EAS
AF:
0.277
Gnomad SAS
AF:
0.269
Gnomad FIN
AF:
0.324
Gnomad MID
AF:
0.320
Gnomad NFE
AF:
0.337
Gnomad OTH
AF:
0.382
GnomAD2 exomes
AF:
0.329
AC:
82547
AN:
250626
AF XY:
0.324
show subpopulations
Gnomad AFR exome
AF:
0.655
Gnomad AMR exome
AF:
0.258
Gnomad ASJ exome
AF:
0.363
Gnomad EAS exome
AF:
0.257
Gnomad FIN exome
AF:
0.330
Gnomad NFE exome
AF:
0.328
Gnomad OTH exome
AF:
0.334
GnomAD4 exome
AF:
0.340
AC:
490337
AN:
1442824
Hom.:
86077
Cov.:
29
AF XY:
0.337
AC XY:
242514
AN XY:
718964
show subpopulations
Gnomad4 AFR exome
AF:
0.659
AC:
21814
AN:
33098
Gnomad4 AMR exome
AF:
0.265
AC:
11840
AN:
44646
Gnomad4 ASJ exome
AF:
0.365
AC:
9490
AN:
26000
Gnomad4 EAS exome
AF:
0.344
AC:
13629
AN:
39578
Gnomad4 SAS exome
AF:
0.275
AC:
23635
AN:
85794
Gnomad4 FIN exome
AF:
0.327
AC:
17436
AN:
53382
Gnomad4 NFE exome
AF:
0.337
AC:
369221
AN:
1094808
Gnomad4 Remaining exome
AF:
0.354
AC:
21146
AN:
59778
Heterozygous variant carriers
0
15588
31176
46765
62353
77941
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
11938
23876
35814
47752
59690
<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:
0.414
AC:
62919
AN:
151984
Hom.:
14627
Cov.:
31
AF XY:
0.410
AC XY:
30426
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.644
AC:
0.644419
AN:
0.644419
Gnomad4 AMR
AF:
0.304
AC:
0.304319
AN:
0.304319
Gnomad4 ASJ
AF:
0.381
AC:
0.381268
AN:
0.381268
Gnomad4 EAS
AF:
0.277
AC:
0.277477
AN:
0.277477
Gnomad4 SAS
AF:
0.270
AC:
0.269502
AN:
0.269502
Gnomad4 FIN
AF:
0.324
AC:
0.32373
AN:
0.32373
Gnomad4 NFE
AF:
0.337
AC:
0.337145
AN:
0.337145
Gnomad4 OTH
AF:
0.379
AC:
0.378802
AN:
0.378802
Heterozygous variant carriers
0
1738
3476
5214
6952
8690
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
566
1132
1698
2264
2830
<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:
0.364
Hom.:
5384
Bravo
AF:
0.422
Asia WGS
AF:
0.278
AC:
967
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Nov 10, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
5.9
DANN
Benign
0.48
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Mutation Taster
=100/0
polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138156; hg19: chr22-46114398; COSMIC: COSV53294235; COSMIC: COSV53294235; API