Variant 9-32973357-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001195248.2(APTX):c.*141G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 995,456 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

APTX
NM_001195248.2 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.315

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 9-32973357-C-T is Benign according to our data. Variant chr9-32973357-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 915132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00411 (626/152234) while in subpopulation AFR AF= 0.0144 (598/41534). AF 95% confidence interval is 0.0134. There are 6 homozygotes in gnomad4. There are 290 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APTX	NM_001195248.2 linkuse as main transcript	c.*141G>A		3_prime_UTR_variant	8/8	ENST00000379817.7	NP_001182177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000379817.7 linkuse as main transcript	c.*141G>A		3_prime_UTR_variant	8/8	1	NM_001195248.2	ENSP00000369145	P1	Q7Z2E3-7

Frequencies

GnomAD3 genomes

AF:

0.00411

AC:

625

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000995

AC:

182

AN:

182884

Hom.:

AF XY:

0.000729

AC XY:

AN XY:

100126

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.000601

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000381

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000509

Gnomad OTH exome

AF:

0.000400

GnomAD4 exome

AF:

0.000458

AC:

386

AN:

843222

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

168

AN XY:

440706

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.000600

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000427

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000331

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00411

AC:

626

AN:

152234

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

290

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.00507

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 24, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

DANN

Benign

0.50

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.

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