9-32925000-G-T

Position:

• chr9-32925000-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000672846.1(APTX):​c.*952C>A variant causes a 3 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,016 control chromosomes in the GnomAD database, including 4,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4250 hom., cov: 32)
• Consequence: APTX ENST00000672846.1 3_prime_UTR, NMD_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0250

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 9-32925000-G-T is Benign according to our data. Variant chr9-32925000-G-T is described in ClinVar as [Benign]. Clinvar id is 3256809.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000672846.1	c.*952C>A		3_prime_UTR_variant, NMD_transcript_variant	10/11			ENSP00000500396

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34995 AN: 151896 Hom.: 4244 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 35031 AN: 152016 Hom.: 4250 Cov.: 32 AF XY: 0.227 AC XY: 16886 AN XY: 74336

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.0292

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.232

Alfa AF: 0.143 Hom.: 248

Bravo AF: 0.229

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 44. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12348381; hg19: chr9-32924998;