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GeneBe

22-45689757-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_013236.4(ATXN10):c.162A>G(p.Leu54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000917 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

ATXN10
NM_013236.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.148
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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 22-45689757-A-G is Benign according to our data. Variant chr22-45689757-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3044990.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.148 with no splicing effect.
BS2
High AC in GnomAd at 70 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATXN10NM_013236.4 linkuse as main transcriptc.162A>G p.Leu54= synonymous_variant 2/12 ENST00000252934.10
ATXN10XM_047441314.1 linkuse as main transcriptc.162A>G p.Leu54= synonymous_variant 2/12
ATXN10NM_001167621.2 linkuse as main transcriptc.117-3239A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATXN10ENST00000252934.10 linkuse as main transcriptc.162A>G p.Leu54= synonymous_variant 2/121 NM_013236.4 P1Q9UBB4-1
ATXN10ENST00000381061.8 linkuse as main transcriptc.117-3239A>G intron_variant 2 Q9UBB4-2
ATXN10ENST00000470722.1 linkuse as main transcriptn.121A>G non_coding_transcript_exon_variant 2/43
ATXN10ENST00000498009.5 linkuse as main transcriptn.336A>G non_coding_transcript_exon_variant 2/65

Frequencies

GnomAD3 genomes
AF:
0.000460
AC:
70
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000115
AC:
29
AN:
251430
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.00154
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000534
AC:
78
AN:
1461888
Hom.:
0
Cov.:
32
AF XY:
0.0000550
AC XY:
40
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00161
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000460
AC:
70
AN:
152324
Hom.:
0
Cov.:
32
AF XY:
0.000443
AC XY:
33
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00144
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000232
Hom.:
0
Bravo
AF:
0.000468
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

ATXN10-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 06, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
Cadd
Benign
1.8
Dann
Benign
0.36
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8

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: rs140005836; hg19: chr22-46085637; API