Genetic Variant APTX:c.771-13_771-12dupTT (chr9-32974572-G-GAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP6_Very_StrongBS1

The NM_001195248.2(APTX):c.771-13_771-12dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00683 in 1,326,036 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0077 ( 1 hom. )

Consequence

APTX
NM_001195248.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 9-32974572-G-GAA is Benign according to our data. Variant chr9-32974572-G-GAA is described in ClinVar as [Benign]. Clinvar id is 235248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000397 (60/151200) while in subpopulation EAS AF= 0.00934 (48/5138). AF 95% confidence interval is 0.00724. There are 0 homozygotes in gnomad4. There are 36 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APTX	NM_001195248.2 link	c.771-13_771-12dupTT		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.771-13_771-12dupTT		intron_variant	Intron 6 of 7	1	NM_001195248.2	ENSP00000369145.2		Q7Z2E3-7

Frequencies

GnomAD3 genomes

AF:

0.000397

AC:

AN:

151088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00932

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.0000968

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000481

GnomAD4 exome

AF:

0.00766

AC:

8996

AN:

1174836

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

4249

AN XY:

592628

show subpopulations

Gnomad4 AFR exome

AF:

0.00441

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.00340

Gnomad4 EAS exome

AF:

0.0143

Gnomad4 SAS exome

AF:

0.00565

Gnomad4 FIN exome

AF:

0.00531

Gnomad4 NFE exome

AF:

0.00813

Gnomad4 OTH exome

AF:

0.00778

GnomAD4 genome

AF:

0.000397

AC:

AN:

151200

Hom.:

Cov.:

AF XY:

0.000488

AC XY:

AN XY:

73812

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00934

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.0000968

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000477

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 13, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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