rs141493373
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001195248.2(APTX):c.971A>T(p.Gln324Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00199 in 1,614,116 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 4 hom. )
Consequence
APTX
NM_001195248.2 missense
NM_001195248.2 missense
Scores
1
4
8
Clinical Significance
Conservation
PhyloP100: 6.73
Genes affected
APTX (HGNC:15984): (aprataxin) This gene encodes a member of the histidine triad (HIT) superfamily. The encoded protein may play a role in single-stranded DNA repair through its nucleotide-binding activity and its diadenosine polyphosphate hydrolase activity. Mutations in this gene have been associated with ataxia-ocular apraxia. Alternatively spliced transcript variants have been identified for this gene.[provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013023466).
BP6
?
Variant 9-32973556-T-A is Benign according to our data. Variant chr9-32973556-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 136416.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=4, Benign=1}. Variant chr9-32973556-T-A is described in Lovd as [Likely_benign]. Variant chr9-32973556-T-A is described in Lovd as [Benign].
BS2
?
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APTX | NM_001195248.2 | c.971A>T | p.Gln324Leu | missense_variant | 8/8 | ENST00000379817.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APTX | ENST00000379817.7 | c.971A>T | p.Gln324Leu | missense_variant | 8/8 | 1 | NM_001195248.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00118 AC: 179AN: 152120Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00113 AC: 283AN: 251214Hom.: 0 AF XY: 0.00118 AC XY: 160AN XY: 135752
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GnomAD4 exome AF: 0.00207 AC: 3031AN: 1461878Hom.: 4 Cov.: 32 AF XY: 0.00197 AC XY: 1433AN XY: 727238
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GnomAD4 genome ? AF: 0.00118 AC: 179AN: 152238Hom.: 1 Cov.: 32 AF XY: 0.00101 AC XY: 75AN XY: 74432
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:4Benign:7
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 16, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Coenzyme Q10 deficiency, Oculomotor Apraxia Type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
APTX-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 17, 2020 | This 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;.;T;.;.;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Benign
T
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
0.022, 0.0090, 0.0060
.;B;B;.;B;.;.;.;.
Vest4
MVP
MPC
0.077
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