9-32891932-T-C

Position:

• chr9-32891932-T-C

Variant summary

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

The ENST00000672846.1(APTX):​c.*1056-4686A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,056 control chromosomes in the GnomAD database, including 36,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (36392 hom., cov: 32)
• Consequence: APTX ENST00000672846.1 intron, NMD_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.239

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=-0.91).
• BP6: Variant 9-32891932-T-C is Benign according to our data. Variant chr9-32891932-T-C is described in ClinVar as [Benign]. Clinvar id is 3256851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 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.*1056-4686A>G		intron_variant, NMD_transcript_variant				ENSP00000500396

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104044 AN: 151938 Hom.: 36372 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.685 AC: 104124 AN: 152056 Hom.: 36392 Cov.: 32 AF XY: 0.676 AC XY: 50233 AN XY: 74328

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.700

Alfa AF: 0.718 Hom.: 4913

Bravo AF: 0.675

Asia WGS AF: 0.524 AC: 1823 AN: 3476

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 78% 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: 73. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10115224; hg19: chr9-32891930; COSMIC: COSV60352196;