Genetic Variant APTX:n.*389-19012T>A (chr9-32966630-A-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000672519.1(APTX):n.*389-19012T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 152,242 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.040 ( 152 hom., cov: 32)

Consequence

APTX
ENST00000672519.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21

Publications

2 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Genomics England PanelApp

APTX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-32966630-A-T is Benign according to our data. Variant chr9-32966630-A-T is described in ClinVar as Benign. ClinVar VariationId is 3256840.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000672519.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APTX	ENST00000672519.1		n.*389-19012T>A		intron	N/A	ENSP00000500320.1	Q7Z2E3-12
	APTX	ENST00000672846.1		n.*923+46T>A		intron	N/A	ENSP00000500396.1	Q7Z2E3-12

Frequencies

GnomAD3 genomes

AF:

0.0397

AC:

6037

AN:

152124

Hom.:

152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.0581

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.0396

Gnomad FIN

AF:

0.0333

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0297

Gnomad OTH

AF:

0.0401

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0397

AC:

6039

AN:

152242

Hom.:

152

Cov.:

AF XY:

0.0418

AC XY:

3115

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0413

AC:

1714

AN:

41544

American (AMR)

AF:

0.0581

AC:

888

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

AN:

3472

East Asian (EAS)

AF:

0.113

AC:

586

AN:

5186

South Asian (SAS)

AF:

0.0398

AC:

192

AN:

4824

European-Finnish (FIN)

AF:

0.0333

AC:

353

AN:

10610

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0296

AC:

2016

AN:

68004

Other (OTH)

AF:

0.0397

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

284

568

853

1137

1421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0323

Hom.:

Bravo

AF:

0.0417

Asia WGS

AF:

0.0750

AC:

260

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.3

(source)

DANN

Benign

0.79

PhyloP100

1.2

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over