rs10124207

Variant names:

• chr9-32891948-C-G
• rs10124207
• ENST00000672846.1:n.*1056-4702G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000672846.1(APTX):​n.*1056-4702G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,044 control chromosomes in the GnomAD database, including 36,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (36395 hom., cov: 32)
• Consequence: APTX ENST00000672846.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.669
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-32891948-C-G is Benign according to our data. Variant chr9-32891948-C-G is described in ClinVar as Benign. ClinVar VariationId is 3256849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000672846.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APTX	ENST00000672846.1		n.*1056-4702G>C		intron	N/A	ENSP00000500396.1	Q7Z2E3-12

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104059 AN: 151926 Hom.: 36375 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.685 AC: 104139 AN: 152044 Hom.: 36395 Cov.: 32 AF XY: 0.676 AC XY: 50238 AN XY: 74322

African (AFR) AF: 0.644 AC: 26692 AN: 41460

American (AMR) AF: 0.604 AC: 9233 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2314 AN: 3466

East Asian (EAS) AF: 0.312 AC: 1614 AN: 5180

South Asian (SAS) AF: 0.703 AC: 3382 AN: 4812

European-Finnish (FIN) AF: 0.669 AC: 7071 AN: 10566

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51475 AN: 67972

Other (OTH) AF: 0.700 AC: 1475 AN: 2108

Alfa AF: 0.718 Hom.: 4912

Bravo AF: 0.675

Asia WGS AF: 0.524 AC: 1822 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs10124207; hg19: chr9-32891946; COSMIC: COSV60352202;