rs12377462

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.737

Alfa AF: 0.799 Hom.: 57742

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12377462; hg19: chr9-32914589;