9-32986032-TAAAAAAAAA-TAAAAAAAAAA

Variant names:

• chr9-32986032-T-TA
• rs373304582
• NM_001195248.2:c.484-3dupT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001195248.2(APTX):​c.484-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0014 (3 hom.)
• Consequence: APTX NM_001195248.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.384

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 -10 ACMG points.

• BP6: Variant 9-32986032-T-TA is Benign according to our data. Variant chr9-32986032-T-TA is described in ClinVar as [Benign]. Clinvar id is 2767545.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0203 (289/14240) while in subpopulation AFR AF= 0.0532 (270/5078). AF 95% confidence interval is 0.048. There are 0 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APTX	NM_001195248.2	c.484-3dupT		splice_region_variant, 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.484-3_484-2insT		splice_region_variant, intron_variant	Intron 4 of 7	1	NM_001195248.2	ENSP00000369145.2

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 288 AN: 14246 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00847

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.00862

GnomAD4 exome AF: 0.00145 AC: 1038 AN: 717576 Hom.: 3 Cov.: 10 AF XY: 0.00152 AC XY: 563 AN XY: 370954

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.00218

Gnomad4 ASJ exome AF: 0.00106

Gnomad4 EAS exome AF: 0.00172

Gnomad4 SAS exome AF: 0.00354

Gnomad4 FIN exome AF: 0.000528

Gnomad4 NFE exome AF: 0.000854

Gnomad4 OTH exome AF: 0.00183

GnomAD4 genome AF: 0.0203 AC: 289 AN: 14240 Hom.: 0 Cov.: 0 AF XY: 0.0203 AC XY: 134 AN XY: 6598

Gnomad4 AFR AF: 0.0532

Gnomad4 AMR AF: 0.00853

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.00847

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 11, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs373304582; hg19: chr9-32986030;