9-32966630-A-T

Position:

• chr9-32966630-A-T

Variant summary

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

The ENST00000672519.1(APTX):​c.*389-19012T>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 152,242 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.040 (152 hom., cov: 32)
• Consequence: APTX ENST00000672519.1 intron, NMD_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

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=-0.83).
• BP6: Variant 9-32966630-A-T is Benign according to our data. Variant chr9-32966630-A-T is described in ClinVar as [Benign]. Clinvar id is 3256840.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 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	ENST00000672519.1	c.*389-19012T>A		intron_variant, NMD_transcript_variant				ENSP00000500320
APTX	ENST00000672846.1	c.*923+46T>A		intron_variant, NMD_transcript_variant				ENSP00000500396

Frequencies

GnomAD3 genomes AF: 0.0397 AC: 6037 AN: 152124 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0581

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0396

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0401

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

GnomAD4 genome AF: 0.0397 AC: 6039 AN: 152242 Hom.: 152 Cov.: 32 AF XY: 0.0418 AC XY: 3115 AN XY: 74446

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.0581

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.0296

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0323 Hom.: 10

Bravo AF: 0.0417

Asia WGS AF: 0.0750 AC: 260 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 20% 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: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.3
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs80154620; hg19: chr9-32966628;