rs754565169

Variant names:

• chr9-32986042-AC-A
• rs754565169
• NM_001195248.2:c.484-13delG

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001195248.2(APTX):​c.484-13delG variant causes a 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 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.353
• Publications: 0 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 -12 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 VariationId is 402383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APTX	NM_001195248.2	c.484-13delG		intron_variant	Intron 4 of 7	ENST00000379817.7	NP_001182177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000379817.7	c.484-13delG		intron_variant	Intron 4 of 7	1	NM_001195248.2	ENSP00000369145.2

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

GnomAD2 exomes AF: 0.00125 AC: 203 AN: 162686 AF XY: 0.00100

Gnomad AFR exome AF: 0.00944

Gnomad AMR exome AF: 0.000531

Gnomad ASJ exome AF: 0.000150

Gnomad EAS exome AF: 0.000251

Gnomad FIN exome AF: 0.000652

Gnomad NFE exome AF: 0.000784

Gnomad OTH exome AF: 0.00129

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0152 AC: 242 AN: 15928

American (AMR) AF: 0.00136 AC: 30 AN: 22074

Ashkenazi Jewish (ASJ) AF: 0.000515 AC: 7 AN: 13586

East Asian (EAS) AF: 0.000500 AC: 15 AN: 30022

South Asian (SAS) AF: 0.00109 AC: 58 AN: 53288

European-Finnish (FIN) AF: 0.000177 AC: 5 AN: 28236

Middle Eastern (MID) AF: 0.00169 AC: 4 AN: 2368

European-Non Finnish (NFE) AF: 0.000390 AC: 235 AN: 602962

Other (OTH) AF: 0.00144 AC: 49 AN: 34082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00135 AC: 34 AN: 25266

American (AMR) AF: 0.000177 AC: 2 AN: 11272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2674

East Asian (EAS) AF: 0.000226 AC: 1 AN: 4422

South Asian (SAS) AF: 0.00 AC: 0 AN: 3880

European-Finnish (FIN) AF: 0.000353 AC: 2 AN: 5670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.000147 AC: 8 AN: 54452

Other (OTH) AF: 0.00 AC: 0 AN: 1558

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000116344), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Dec 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism

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: rs754565169; hg19: chr9-32986040;