9-32986032-T-TAAAAAAAAAC

Variant names:

• chr9-32986032-T-TAAAAAAAAAC
• rs1554664711
• NM_001195248.2:c.484-3_484-2insGTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001195248.2(APTX):​c.484-3_484-2insGTTTTTTTTT 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00026 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: APTX NM_001195248.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.484-3_484-2insGTTTTTTTTT		splice_region intron	N/A	NP_001182177.2	Q7Z2E3-7
	APTX	NM_001195249.2		c.484-3_484-2insGTTTTTTTTT		splice_region intron	N/A	NP_001182178.1	Q7Z2E3-7
	APTX	NM_001368995.1		c.484-3_484-2insGTTTTTTTTT		splice_region 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.484-3_484-2insGTTTTTTTTT		splice_region intron	N/A	ENSP00000369145.2	Q7Z2E3-7
	APTX	ENST00000379819.6	TSL:1	c.484-3_484-2insGTTTTTTTTT		splice_region intron	N/A	ENSP00000369147.2	Q7Z2E3-7
	APTX	ENST00000463596.6	TSL:1	c.484-3_484-2insGTTTTTTTTT		splice_region intron	N/A	ENSP00000419846.1	Q7Z2E3-7

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 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: 0.00

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: 0.000262 AC: 188 AN: 718864 Hom.: 2 Cov.: 10 AF XY: 0.000299 AC XY: 111 AN XY: 371608

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

African (AFR) AF: 0.000453 AC: 7 AN: 15458

American (AMR) AF: 0.000806 AC: 20 AN: 24812

Ashkenazi Jewish (ASJ) AF: 0.000248 AC: 4 AN: 16120

East Asian (EAS) AF: 0.000941 AC: 23 AN: 24452

South Asian (SAS) AF: 0.000835 AC: 43 AN: 51520

European-Finnish (FIN) AF: 0.000105 AC: 3 AN: 28444

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

European-Non Finnish (NFE) AF: 0.000153 AC: 80 AN: 523950

Other (OTH) AF: 0.000252 AC: 8 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 14400 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

Splicing

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: rs1554664711;

hg19: chr9-32986030;