rs200922655

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000379817.7(APTX):​c.484-25_484-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,277,180 control chromosomes in the GnomAD database, including 14,600 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 7125 hom., cov: 0)
Exomes 𝑓: 0.27 ( 7475 hom. )

Consequence

APTX
ENST00000379817.7 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.13
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 9-32986034-AAAAAAAAACAAAAAAAAAAAC-A is Benign according to our data. Variant chr9-32986034-AAAAAAAAACAAAAAAAAAAAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 198285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-32986034-AAAAAAAAACAAAAAAAAAAAC-A is described in Lovd as [Likely_benign]. Variant chr9-32986034-AAAAAAAAACAAAAAAAAAAAC-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
APTXNM_001195248.2 linkuse as main transcriptc.484-25_484-5del splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000379817.7 NP_001182177.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APTXENST00000379817.7 linkuse as main transcriptc.484-25_484-5del splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_001195248.2 ENSP00000369145 P1Q7Z2E3-7

Frequencies

GnomAD3 genomes
AF:
0.421
AC:
44470
AN:
105626
Hom.:
7126
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.328
Gnomad AMI
AF:
0.557
Gnomad AMR
AF:
0.430
Gnomad ASJ
AF:
0.524
Gnomad EAS
AF:
0.248
Gnomad SAS
AF:
0.296
Gnomad FIN
AF:
0.442
Gnomad MID
AF:
0.436
Gnomad NFE
AF:
0.477
Gnomad OTH
AF:
0.443
GnomAD4 exome
AF:
0.266
AC:
311082
AN:
1171552
Hom.:
7475
AF XY:
0.261
AC XY:
152703
AN XY:
586162
show subpopulations
Gnomad4 AFR exome
AF:
0.189
Gnomad4 AMR exome
AF:
0.220
Gnomad4 ASJ exome
AF:
0.310
Gnomad4 EAS exome
AF:
0.111
Gnomad4 SAS exome
AF:
0.137
Gnomad4 FIN exome
AF:
0.245
Gnomad4 NFE exome
AF:
0.286
Gnomad4 OTH exome
AF:
0.257
GnomAD4 genome
AF:
0.421
AC:
44465
AN:
105628
Hom.:
7125
Cov.:
0
AF XY:
0.416
AC XY:
21038
AN XY:
50558
show subpopulations
Gnomad4 AFR
AF:
0.328
Gnomad4 AMR
AF:
0.430
Gnomad4 ASJ
AF:
0.524
Gnomad4 EAS
AF:
0.248
Gnomad4 SAS
AF:
0.295
Gnomad4 FIN
AF:
0.442
Gnomad4 NFE
AF:
0.477
Gnomad4 OTH
AF:
0.442
Alfa
AF:
0.283
Hom.:
259

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Dec 02, 2014- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsJun 09, 2017- -
not provided Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxJun 11, 2018- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Benign, no assertion criteria providedclinical testingMayo Clinic Laboratories, Mayo ClinicMar 09, 2016- -
Coenzyme Q10 deficiency, Oculomotor Apraxia Type Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesNov 29, 2023- -
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs200922655; hg19: chr9-32986032; API