9-32974572-GAAA-GAAAA

Variant names:

• chr9-32974572-G-GA
• rs34600530
• NM_001195248.2:c.771-12dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001195248.2(APTX):​c.771-12dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,367,140 control chromosomes in the GnomAD database, including 236,383 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29841 hom., cov: 0)
  • Exomes 𝑓: 0.59 (206542 hom.)
• Consequence: APTX NM_001195248.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.0780
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 9-32974572-G-GA is Benign according to our data. Variant chr9-32974572-G-GA is described in ClinVar as Benign. ClinVar VariationId is 214123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94340 AN: 151052 Hom.: 29824 Cov.: 0

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.631

GnomAD2 exomes AF: 0.643 AC: 138712 AN: 215722 AF XY: 0.650

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.666

Gnomad ASJ exome AF: 0.539

Gnomad EAS exome AF: 0.851

Gnomad FIN exome AF: 0.648

Gnomad NFE exome AF: 0.597

Gnomad OTH exome AF: 0.615

GnomAD4 exome AF: 0.592 AC: 720026 AN: 1215976 Hom.: 206542 Cov.: 22 AF XY: 0.600 AC XY: 369092 AN XY: 614714

African (AFR) AF: 0.489 AC: 14178 AN: 28972

American (AMR) AF: 0.659 AC: 27967 AN: 42436

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 12849 AN: 24088

East Asian (EAS) AF: 0.808 AC: 28961 AN: 35840

South Asian (SAS) AF: 0.769 AC: 59732 AN: 77694

European-Finnish (FIN) AF: 0.633 AC: 28050 AN: 44336

Middle Eastern (MID) AF: 0.575 AC: 2858 AN: 4970

European-Non Finnish (NFE) AF: 0.568 AC: 514572 AN: 905916

Other (OTH) AF: 0.597 AC: 30859 AN: 51724

GnomAD4 genome AF: 0.624 AC: 94388 AN: 151164 Hom.: 29841 Cov.: 0 AF XY: 0.632 AC XY: 46638 AN XY: 73784

African (AFR) AF: 0.538 AC: 22166 AN: 41192

American (AMR) AF: 0.659 AC: 10022 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1994 AN: 3462

East Asian (EAS) AF: 0.863 AC: 4436 AN: 5140

South Asian (SAS) AF: 0.836 AC: 4005 AN: 4788

European-Finnish (FIN) AF: 0.677 AC: 6994 AN: 10326

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42788 AN: 67760

Other (OTH) AF: 0.635 AC: 1331 AN: 2096

Alfa AF: 0.545 Hom.: 2452

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (1)
-	-	1	Coenzyme Q10 deficiency, Oculomotor Apraxia Type (1)
-	-	1	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.078
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34600530; hg19: chr9-32974570;