rs10758179

chr9-33023835-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000468275.6(APTX):c.-5+969A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,260 control chromosomes in the GnomAD database, including 1,474 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 0.13 (1474 hom., cov: 33)
• Consequence: APTX ENST00000468275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APTX	NM_001368995.1	c.-5+1165A>G		intron_variant
APTX	NM_001368996.1	c.-5+1188A>G		intron_variant
APTX	NM_001368997.1	c.-5+969A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APTX	ENST00000436040.7	c.-5+1188A>G		intron_variant		1
APTX	ENST00000468275.6	c.-5+969A>G		intron_variant		1
APTX	ENST00000460940.6	c.-5+1165A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19854 AN: 152142 Hom.: 1472 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0705

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.130 AC: 19869 AN: 152260 Hom.: 1474 Cov.: 33 AF XY: 0.131 AC XY: 9742 AN XY: 74442

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.0705

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.105

Alfa AF: 0.110 Hom.: 1943

Bravo AF: 0.131

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.9
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10758179; hg19: chr9-33023833; COSMIC: COSV58309956;