NM_001195248.2:c.484-12_484-3dupTTTTTTTTTT

Variant names:

• chr9-32986032-T-TAAAAAAAAAA
• rs373304582
• NM_001195248.2:c.484-12_484-3dupTTTTTTTTTT

Variant summary

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

The NM_001195248.2(APTX):​c.484-12_484-3dupTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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: 0.384
• 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APTX	NM_001195248.2	c.484-12_484-3dupTTTTTTTTTT		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.484-3_484-2insTTTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 7	1	NM_001195248.2	ENSP00000369145.2

Frequencies

GnomAD3 genomes AF: 0.0000695 AC: 1 AN: 14394 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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: 718916 Hom.: 0 Cov.: 10 AF XY: 0.00000269 AC XY: 1 AN XY: 371642

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15444

American (AMR) AF: 0.00 AC: 0 AN: 24810

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 24462

South Asian (SAS) AF: 0.0000194 AC: 1 AN: 51542

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: 523986

Other (OTH) AF: 0.00 AC: 0 AN: 31800

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000695 AC: 1 AN: 14394 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6656

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000194 AC: 1 AN: 5152

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

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 468

South Asian (SAS) AF: 0.00 AC: 0 AN: 388

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

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;