rs754565169

Positions:

• chr9-32986042-AC-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001195248.2(APTX):​c.484-13del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 19)
  • Exomes 𝑓: 0.00080 (8 hom.)
• Consequence: APTX NM_001195248.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.353

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 9-32986042-AC-A is Benign according to our data. Variant chr9-32986042-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 402383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-32986042-AC-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000804 (645/802546) while in subpopulation AFR AF= 0.0152 (242/15928). AF 95% confidence interval is 0.0136. There are 8 homozygotes in gnomad4_exome. There are 314 alleles in male gnomad4_exome subpopulation. Median coverage is 16. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APTX	NM_001195248.2	c.484-13del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000379817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APTX	ENST00000379817.7	c.484-13del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001195248.2	P1

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 47 AN: 110118 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00131

Gnomad AMI AF: 0.00145

Gnomad AMR AF: 0.000178

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000225

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000353

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000804 AC: 645 AN: 802546 Hom.: 8 Cov.: 16 AF XY: 0.000773 AC XY: 314 AN XY: 406180

Gnomad4 AFR exome AF: 0.0152

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.000515

Gnomad4 EAS exome AF: 0.000500

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.000177

Gnomad4 NFE exome AF: 0.000390

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.000436 AC: 48 AN: 110108 Hom.: 0 Cov.: 19 AF XY: 0.000455 AC XY: 24 AN XY: 52772

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.000177

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000226

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000353

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely 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: Similar deletions very frequent in ExAC -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs754565169; hg19: chr9-32986040;