9-32978808-C-T

Variant names:

• chr9-32978808-C-T
• rs10971259
• NM_001195248.2:c.771-4247G>A

Variant summary

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

The NM_001195248.2(APTX):​c.771-4247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,086 control chromosomes in the GnomAD database, including 2,461 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 0.17 (2461 hom., cov: 32)
• Consequence: APTX NM_001195248.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 11 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, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195248.2. 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_001195248.2	MANE Select	c.771-4247G>A		intron	N/A	NP_001182177.2	Q7Z2E3-7
	APTX	NM_001195249.2		c.771-4247G>A		intron	N/A	NP_001182178.1	Q7Z2E3-7
	APTX	NM_001368995.1		c.771-4247G>A		intron	N/A	NP_001355924.1	Q7Z2E3-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APTX	ENST00000379817.7	TSL:1 MANE Select	c.771-4247G>A		intron	N/A	ENSP00000369145.2	Q7Z2E3-7
	APTX	ENST00000379819.6	TSL:1	c.771-4247G>A		intron	N/A	ENSP00000369147.2	Q7Z2E3-7
	APTX	ENST00000463596.6	TSL:1	c.771-4247G>A		intron	N/A	ENSP00000419846.1	Q7Z2E3-7

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26095 AN: 151968 Hom.: 2454 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.172 AC: 26149 AN: 152086 Hom.: 2461 Cov.: 32 AF XY: 0.174 AC XY: 12956 AN XY: 74356

African (AFR) AF: 0.214 AC: 8885 AN: 41478

American (AMR) AF: 0.158 AC: 2415 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3466

East Asian (EAS) AF: 0.407 AC: 2097 AN: 5156

South Asian (SAS) AF: 0.234 AC: 1128 AN: 4822

European-Finnish (FIN) AF: 0.102 AC: 1079 AN: 10590

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9602 AN: 67968

Other (OTH) AF: 0.159 AC: 336 AN: 2112

Alfa AF: 0.147 Hom.: 2958

Bravo AF: 0.175

Asia WGS AF: 0.301 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.60
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10971259;

hg19: chr9-32978806;

COSMIC: COSV58928119;

COSMIC: COSV58928119;