rs200922655

Positions:

• chr9-32986034-AAAAAAAAACAAAAAAAAAAAC-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001195248.2(APTX):​c.484-25_484-5delGTTTTTTTTTTTGTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,277,180 control chromosomes in the GnomAD database, including 14,600 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (7125 hom., cov: 0)
  • Exomes 𝑓: 0.27 (7475 hom.)
• Consequence: APTX NM_001195248.2 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.13

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 9-32986034-AAAAAAAAACAAAAAAAAAAAC-A is Benign according to our data. Variant chr9-32986034-AAAAAAAAACAAAAAAAAAAAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 198285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-32986034-AAAAAAAAACAAAAAAAAAAAC-A is described in Lovd as [Likely_benign]. Variant chr9-32986034-AAAAAAAAACAAAAAAAAAAAC-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APTX	NM_001195248.2	c.484-25_484-5delGTTTTTTTTTTTGTTTTTTTT		splice_region_variant, intron_variant		ENST00000379817.7	NP_001182177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000379817.7	c.484-25_484-5delGTTTTTTTTTTTGTTTTTTTT		splice_region_variant, intron_variant		1	NM_001195248.2	ENSP00000369145.2

Frequencies

GnomAD3 genomes AF: 0.421 AC: 44470 AN: 105626 Hom.: 7126 Cov.: 0

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.266 AC: 311082 AN: 1171552 Hom.: 7475 AF XY: 0.261 AC XY: 152703 AN XY: 586162

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.421 AC: 44465 AN: 105628 Hom.: 7125 Cov.: 0 AF XY: 0.416 AC XY: 21038 AN XY: 50558

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.442

Alfa AF: 0.283 Hom.: 259

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 02, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 09, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 09, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2018	- -

Coenzyme Q10 deficiency, Oculomotor Apraxia Type Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200922655; hg19: chr9-32986032;