Genetic Variant APTX:c.771-12dupT (chr9-32974572-G-GA) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_001195248.2(APTX):c.771-12dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,367,140 control chromosomes in the GnomAD database, including 236,383 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29841 hom., cov: 0)

Exomes 𝑓: 0.59 ( 206542 hom. )

Consequence

APTX
NM_001195248.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.0780

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-32974572-G-GA is Benign according to our data. Variant chr9-32974572-G-GA is described in ClinVar as [Benign]. Clinvar id is 214123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APTX	NM_001195248.2 link	c.771-12dupT		intron_variant	Intron 6 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.771-12dupT		intron_variant	Intron 6 of 7	1	NM_001195248.2	ENSP00000369145.2		Q7Z2E3-7

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

94340

AN:

151052

Hom.:

29824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.659

Gnomad ASJ

AF:

0.576

Gnomad EAS

AF:

0.863

Gnomad SAS

AF:

0.837

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.631

Gnomad OTH

AF:

0.631

GnomAD3 exomes

AF:

0.643

AC:

138712

AN:

215722

Hom.:

43574

AF XY:

0.650

AC XY:

75929

AN XY:

116786

show subpopulations

Gnomad AFR exome

AF:

0.514

Gnomad AMR exome

AF:

0.666

Gnomad ASJ exome

AF:

0.539

Gnomad EAS exome

AF:

0.851

Gnomad SAS exome

AF:

0.792

Gnomad FIN exome

AF:

0.648

Gnomad NFE exome

AF:

0.597

Gnomad OTH exome

AF:

0.615

GnomAD4 exome

AF:

0.592

AC:

720026

AN:

1215976

Hom.:

206542

Cov.:

AF XY:

0.600

AC XY:

369092

AN XY:

614714

show subpopulations

Gnomad4 AFR exome

AF:

0.489

Gnomad4 AMR exome

AF:

0.659

Gnomad4 ASJ exome

AF:

0.533

Gnomad4 EAS exome

AF:

0.808

Gnomad4 SAS exome

AF:

0.769

Gnomad4 FIN exome

AF:

0.633

Gnomad4 NFE exome

AF:

0.568

Gnomad4 OTH exome

AF:

0.597

GnomAD4 genome

AF:

0.624

AC:

94388

AN:

151164

Hom.:

29841

Cov.:

AF XY:

0.632

AC XY:

46638

AN XY:

73784

show subpopulations

Gnomad4 AFR

AF:

0.538

Gnomad4 AMR

AF:

0.659

Gnomad4 ASJ

AF:

0.576

Gnomad4 EAS

AF:

0.863

Gnomad4 SAS

AF:

0.836

Gnomad4 FIN

AF:

0.677

Gnomad4 NFE

AF:

0.631

Gnomad4 OTH

AF:

0.635

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 85% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 79. Only high quality variants are reported. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Disclaimer: This variant has not undergone full assessment. The following are pr eliminary notes: Frequency -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

- -

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

Jul 14, 2021

Genome-Nilou Lab

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

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.

9-32974572-GAAA-GAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over