chr9-32986032-TAAAAAAAAA-T

Variant names:

• chr9-32986032-TAAAAAAAAA-T
• rs373304582
• NM_001195248.2:c.484-11_484-3delTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001195248.2(APTX):​c.484-11_484-3delTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 733,346 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000069 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: APTX NM_001195248.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APTX	NM_001195248.2	c.484-11_484-3delTTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 7	ENST00000379817.7	NP_001182177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000379817.7	c.484-11_484-3delTTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 7	1	NM_001195248.2	ENSP00000369145.2

Frequencies

GnomAD3 genomes AF: 0.0000694 AC: 1 AN: 14400 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00214

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 1 AN: 718946 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 371660

African (AFR) AF: 0.00 AC: 0 AN: 15458

American (AMR) AF: 0.00 AC: 0 AN: 24816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16120

East Asian (EAS) AF: 0.0000409 AC: 1 AN: 24462

South Asian (SAS) AF: 0.00 AC: 0 AN: 51546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 523988

Other (OTH) AF: 0.00 AC: 0 AN: 31804

GnomAD4 genome AF: 0.0000694 AC: 1 AN: 14400 Hom.: 0 Cov.: 0 AF XY: 0.000150 AC XY: 1 AN XY: 6660

African (AFR) AF: 0.00 AC: 0 AN: 5156

American (AMR) AF: 0.00 AC: 0 AN: 1192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 320

East Asian (EAS) AF: 0.00214 AC: 1 AN: 468

South Asian (SAS) AF: 0.00 AC: 0 AN: 390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 48

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6094

Other (OTH) AF: 0.00 AC: 0 AN: 118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

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

Other links and lift over

dbSNP: rs373304582; hg19: chr9-32986030;