Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001195248.2(APTX):c.771-14_771-12delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,369,244 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

APTX
NM_001195248.2 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0780

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: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 9-32974572-GAAA-G is Benign according to our data. Variant chr9-32974572-GAAA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1650542.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195248.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
APTX	NM_001195248.2	MANE Select	c.771-14_771-12delTTT	intron	N/A	NP_001182177.2
APTX	NM_001195249.2		c.771-14_771-12delTTT	intron	N/A	NP_001182178.1
APTX	NM_001368995.1		c.771-14_771-12delTTT	intron	N/A	NP_001355924.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
APTX	ENST00000379817.7	TSL:1 MANE Select	c.771-14_771-12delTTT	intron	N/A	ENSP00000369145.2
APTX	ENST00000379819.6	TSL:1	c.771-14_771-12delTTT	intron	N/A	ENSP00000369147.2
APTX	ENST00000463596.6	TSL:1	c.771-14_771-12delTTT	intron	N/A	ENSP00000419846.1

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

151134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000107

AC:

AN:

215722

AF XY:

0.000120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000101

Gnomad ASJ exome

AF:

0.000771

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000689

Gnomad OTH exome

AF:

0.000373

GnomAD4 exome

AF:

0.0000550

AC:

AN:

1217998

Hom.:

AF XY:

0.0000601

AC XY:

AN XY:

615640

show subpopulations

African (AFR)

AF:

0.0000344

AC:

AN:

29046

American (AMR)

AF:

0.0000941

AC:

AN:

42512

Ashkenazi Jewish (ASJ)

AF:

0.000580

AC:

AN:

24128

East Asian (EAS)

AF:

0.00

AC:

AN:

35850

South Asian (SAS)

AF:

0.000283

AC:

AN:

77764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44424

Middle Eastern (MID)

AF:

0.000402

AC:

AN:

4978

European-Non Finnish (NFE)

AF:

0.0000187

AC:

AN:

907494

Other (OTH)

AF:

0.000135

AC:

AN:

51802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000397

AC:

AN:

151246

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73840

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41220

American (AMR)

AF:

0.0000658

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10344

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000443

AC:

AN:

67786

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000131

Hom.:

2452

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.078

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

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.

rs34600530

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over