chr9-33023835-T-C

Variant names:

• chr9-33023835-T-C
• rs10758179
• ENST00000468275.6:c.-5+969A>G

Variant summary

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

The NM_001368995.1(APTX):​c.-5+1165A>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 NM_001368995.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 2 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368995.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APTX	NM_001368995.1		c.-5+1165A>G		intron	N/A	NP_001355924.1	Q7Z2E3-7
	APTX	NM_001368996.1		c.-5+1188A>G		intron	N/A	NP_001355925.1	Q7Z2E3-7
	APTX	NM_001368997.1		c.-5+969A>G		intron	N/A	NP_001355926.1	Q7Z2E3-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APTX	ENST00000468275.6	TSL:1	c.-5+969A>G		intron	N/A	ENSP00000420263.2	Q7Z2E3-9
	APTX	ENST00000436040.7	TSL:1	c.-5+1188A>G		intron	N/A	ENSP00000400806.4	Q7Z2E3-5
	APTX	ENST00000460940.6	TSL:1	n.-5+1165A>G		intron	N/A	ENSP00000418311.1	Q7Z2E3-12

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

African (AFR) AF: 0.181 AC: 7502 AN: 41528

American (AMR) AF: 0.0846 AC: 1294 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1474 AN: 5188

South Asian (SAS) AF: 0.170 AC: 821 AN: 4824

European-Finnish (FIN) AF: 0.0705 AC: 748 AN: 10610

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7374 AN: 68018

Other (OTH) AF: 0.105 AC: 223 AN: 2116

Alfa AF: 0.115 Hom.: 4730

Bravo AF: 0.131

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.69
PhyloP100		-0.35

Splicing

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

Other links and lift over

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