rs10124051

Variant names:

• chr9-33007413-T-C
• rs10124051
• ENST00000468275.6:c.-5+17391A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-33007413-T-C
• chr9-33007413-T-G

Variant summary

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

The ENST00000468275.6(APTX):​c.-5+17391A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,218 control chromosomes in the GnomAD database, including 1,308 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 0.12 (1308 hom., cov: 32)
• Consequence: APTX ENST00000468275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• 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

ENSG00000305836 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• 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 rank	MANE	Protein	UniProt
APTX	NM_001368995.1	c.-4-17518A>G		intron_variant	Intron 1 of 7		NP_001355924.1
APTX	NM_001368996.1	c.-4-17518A>G		intron_variant	Intron 1 of 7		NP_001355925.1
APTX	NM_001368997.1	c.-5+17391A>G		intron_variant	Intron 1 of 7		NP_001355926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000468275.6	c.-5+17391A>G		intron_variant	Intron 1 of 7	1		ENSP00000420263.2
APTX	ENST00000436040.7	c.-4-17518A>G		intron_variant	Intron 1 of 6	1		ENSP00000400806.4
APTX	ENST00000460940.6	n.-4-17518A>G		intron_variant	Intron 1 of 6	1		ENSP00000418311.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18817 AN: 152100 Hom.: 1307 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.124 AC: 18828 AN: 152218 Hom.: 1308 Cov.: 32 AF XY: 0.124 AC XY: 9264 AN XY: 74418

African (AFR) AF: 0.157 AC: 6528 AN: 41508

American (AMR) AF: 0.0827 AC: 1265 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1473 AN: 5182

South Asian (SAS) AF: 0.170 AC: 819 AN: 4826

European-Finnish (FIN) AF: 0.0704 AC: 746 AN: 10600

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7370 AN: 68020

Other (OTH) AF: 0.101 AC: 213 AN: 2114

Alfa AF: 0.108 Hom.: 1846

Bravo AF: 0.123

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.62

Splicing

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

Other links and lift over

dbSNP: rs10124051; hg19: chr9-33007411;