9-32914591-C-T

Variant names:

• chr9-32914591-C-T
• rs12377462
• ENST00000672846.1:n.*1055+10306G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000672846.1(APTX):​n.*1055+10306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,042 control chromosomes in the GnomAD database, including 39,736 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (39736 hom., cov: 31)
• Consequence: APTX ENST00000672846.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 5 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000672846.1	n.*1055+10306G>A		intron_variant	Intron 10 of 10			ENSP00000500396.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106530 AN: 151924 Hom.: 39733 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.701 AC: 106575 AN: 152042 Hom.: 39736 Cov.: 31 AF XY: 0.701 AC XY: 52089 AN XY: 74314

African (AFR) AF: 0.459 AC: 19037 AN: 41436

American (AMR) AF: 0.771 AC: 11782 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2609 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1767 AN: 5150

South Asian (SAS) AF: 0.854 AC: 4120 AN: 4822

European-Finnish (FIN) AF: 0.792 AC: 8373 AN: 10566

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56374 AN: 68000

Other (OTH) AF: 0.737 AC: 1557 AN: 2112

Alfa AF: 0.773 Hom.: 107114

Bravo AF: 0.684

Asia WGS AF: 0.577 AC: 2010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.62
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs12377462; hg19: chr9-32914589;