Genetic Variant APTX:n.*952C>A (chr9-32925000-G-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 ENST00000672846.1(APTX):n.*952C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,016 control chromosomes in the GnomAD database, including 4,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4250 hom., cov: 32)

Consequence

APTX
ENST00000672846.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0250

Publications

0 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:

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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=-0.76).

BP6

Variant 9-32925000-G-T is Benign according to our data. Variant chr9-32925000-G-T is described in ClinVar as Benign. ClinVar VariationId is 3256809.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000672846.1. 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	ENST00000672846.1		n.*952C>A		non_coding_transcript_exon	Exon 10 of 11	ENSP00000500396.1	Q7Z2E3-12
	APTX	ENST00000672846.1		n.*952C>A		3_prime_UTR	Exon 10 of 11	ENSP00000500396.1	Q7Z2E3-12

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34995

AN:

151896

Hom.:

4244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.0291

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.233

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

GnomAD4 genome

AF:

0.230

AC:

35031

AN:

152016

Hom.:

4250

Cov.:

AF XY:

0.227

AC XY:

16886

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.210

AC:

8702

AN:

41424

American (AMR)

AF:

0.236

AC:

3600

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1083

AN:

3468

East Asian (EAS)

AF:

0.0292

AC:

151

AN:

5174

South Asian (SAS)

AF:

0.111

AC:

533

AN:

4816

European-Finnish (FIN)

AF:

0.264

AC:

2792

AN:

10568

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.257

AC:

17457

AN:

67972

Other (OTH)

AF:

0.232

AC:

489

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1346

2692

4037

5383

6729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.143

Hom.:

248

Bravo

AF:

0.229

Asia WGS

AF:

0.0850

AC:

296

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

-0.76

CADD

Benign

1.3

(source)

DANN

Benign

0.82

PhyloP100

0.025

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over