22-45693025-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_013236.4(ATXN10):āc.338A>Gā(p.Asp113Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 32)
Exomes š: 0.000017 ( 0 hom. )
Consequence
ATXN10
NM_013236.4 missense
NM_013236.4 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 3.92
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18227562).
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATXN10 | NM_013236.4 | c.338A>G | p.Asp113Gly | missense_variant | 3/12 | ENST00000252934.10 | |
ATXN10 | NM_001167621.2 | c.146A>G | p.Asp49Gly | missense_variant | 2/11 | ||
ATXN10 | XM_047441314.1 | c.338A>G | p.Asp113Gly | missense_variant | 3/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATXN10 | ENST00000252934.10 | c.338A>G | p.Asp113Gly | missense_variant | 3/12 | 1 | NM_013236.4 | P1 | |
ATXN10 | ENST00000381061.8 | c.146A>G | p.Asp49Gly | missense_variant | 2/11 | 2 | |||
ATXN10 | ENST00000470722.1 | n.297A>G | non_coding_transcript_exon_variant | 3/4 | 3 | ||||
ATXN10 | ENST00000498009.5 | n.512A>G | non_coding_transcript_exon_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251442Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135898
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461802Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727196
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2021 | The c.338A>G (p.D113G) alteration is located in exon 3 (coding exon 3) of the ATXN10 gene. This alteration results from a A to G substitution at nucleotide position 338, causing the aspartic acid (D) at amino acid position 113 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Benign
T;T;.
Polyphen
0.85
.;P;.
Vest4
MVP
MPC
0.096
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at