9-32986032-T-TAAAAAAAAACAAA

Variant names:

• chr9-32986032-T-TAAAAAAAAACAAA
• rs1554664711
• NM_001195248.2:c.484-3_484-2insTTTGTTTTTTTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001195248.2(APTX):​c.484-3_484-2insTTTGTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00085 (7 hom.)
• Consequence: APTX NM_001195248.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-32986032-T-TAAAAAAAAACAAA is Benign according to our data. Variant chr9-32986032-T-TAAAAAAAAACAAA is described in ClinVar as Likely_benign. ClinVar VariationId is 2112401.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000855 (614/718470) while in subpopulation EAS AF = 0.00364 (89/24424). AF 95% confidence interval is 0.00303. There are 7 homozygotes in GnomAdExome4. There are 330 alleles in the male GnomAdExome4 subpopulation. Median coverage is 10. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 7 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_484-2insTTTGTTTTTTTTT		splice_region intron	N/A	NP_001182177.2	Q7Z2E3-7
	APTX	NM_001195249.2		c.484-3_484-2insTTTGTTTTTTTTT		splice_region intron	N/A	NP_001182178.1	Q7Z2E3-7
	APTX	NM_001368995.1		c.484-3_484-2insTTTGTTTTTTTTT		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_484-2insTTTGTTTTTTTTT		splice_region intron	N/A	ENSP00000369145.2	Q7Z2E3-7
	APTX	ENST00000379819.6	TSL:1	c.484-3_484-2insTTTGTTTTTTTTT		splice_region intron	N/A	ENSP00000369147.2	Q7Z2E3-7
	APTX	ENST00000463596.6	TSL:1	c.484-3_484-2insTTTGTTTTTTTTT		splice_region intron	N/A	ENSP00000419846.1	Q7Z2E3-7

Frequencies

GnomAD3 genomes AF: 0.000139 AC: 2 AN: 14392 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: 0.000164

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000855 AC: 614 AN: 718470 Hom.: 7 Cov.: 10 AF XY: 0.000889 AC XY: 330 AN XY: 371398

African (AFR) AF: 0.00240 AC: 37 AN: 15434

American (AMR) AF: 0.00186 AC: 46 AN: 24796

Ashkenazi Jewish (ASJ) AF: 0.00112 AC: 18 AN: 16106

East Asian (EAS) AF: 0.00364 AC: 89 AN: 24424

South Asian (SAS) AF: 0.00177 AC: 91 AN: 51470

European-Finnish (FIN) AF: 0.000281 AC: 8 AN: 28438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2304

European-Non Finnish (NFE) AF: 0.000554 AC: 290 AN: 523714

Other (OTH) AF: 0.00110 AC: 35 AN: 31784

GnomAD4 genome AF: 0.000139 AC: 2 AN: 14388 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6662

African (AFR) AF: 0.000193 AC: 1 AN: 5170

American (AMR) AF: 0.00 AC: 0 AN: 1184

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 464

South Asian (SAS) AF: 0.00 AC: 0 AN: 386

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 44

European-Non Finnish (NFE) AF: 0.000164 AC: 1 AN: 6088

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

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

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

Other links and lift over

dbSNP: rs1554664711; hg19: chr9-32986030;