rs200922655

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001195248.2(APTX):c.484-25_484-5delGTTTTTTTTTTTGTTTTTTTT variant causes a splice region, 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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
NM_001195248.2 splice_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 2.13

Publications

4 publications found

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]

APTX Gene-Disease associations (from GenCC):

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp

APTX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 198285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
APTX	NM_001195248.2 link	c.484-25_484-5delGTTTTTTTTTTTGTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 7	ENST00000379817.7	NP_001182177.2	Q7Z2E3-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000379817.7 link	c.484-25_484-5delGTTTTTTTTTTTGTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 7	1	NM_001195248.2	ENSP00000369145.2		Q7Z2E3-7

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

44470

AN:

105626

Hom.:

7126

Cov.:

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

GnomAD2 exomes

AF:

0.263

AC:

38489

AN:

146242

AF XY:

0.261

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.266

AC:

311082

AN:

1171552

Hom.:

7475

AF XY:

0.261

AC XY:

152703

AN XY:

586162

show subpopulations

African (AFR)

AF:

0.189

AC:

4795

AN:

25432

American (AMR)

AF:

0.220

AC:

6855

AN:

31152

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

6475

AN:

20866

East Asian (EAS)

AF:

0.111

AC:

3929

AN:

35548

South Asian (SAS)

AF:

0.137

AC:

9419

AN:

68740

European-Finnish (FIN)

AF:

0.245

AC:

9541

AN:

38982

Middle Eastern (MID)

AF:

0.271

AC:

912

AN:

3360

European-Non Finnish (NFE)

AF:

0.286

AC:

256542

AN:

898394

Other (OTH)

AF:

0.257

AC:

12614

AN:

49078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.409

Heterozygous variant carriers

10729

21458

32188

42917

53646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9482

18964

28446

37928

47410

<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:

0.421

AC:

44465

AN:

105628

Hom.:

7125

Cov.:

AF XY:

0.416

AC XY:

21038

AN XY:

50558

show subpopulations

African (AFR)

AF:

0.328

AC:

9345

AN:

28496

American (AMR)

AF:

0.430

AC:

4525

AN:

10530

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1425

AN:

2720

East Asian (EAS)

AF:

0.248

AC:

689

AN:

2780

South Asian (SAS)

AF:

0.295

AC:

797

AN:

2698

European-Finnish (FIN)

AF:

0.442

AC:

2512

AN:

5684

Middle Eastern (MID)

AF:

0.435

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.477

AC:

23992

AN:

50252

Other (OTH)

AF:

0.442

AC:

656

AN:

1484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1328

2656

3983

5311

6639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.283

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

Jun 09, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant 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 -

Dec 02, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 09, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Coenzyme Q10 deficiency, Oculomotor Apraxia Type

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia

Benign:1

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over