9-32986032-T-TAAAAAAAAACAAAA

Position:

• chr9-32986032-T-TAAAAAAAAACAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001195248.2(APTX):​c.484-3_484-2insTTTTGTTTTTTTTT variant causes a splice region, splice polypyrimidine tract, 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: 0.00027 (4 hom.)
• Consequence: APTX NM_001195248.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APTX	NM_001195248.2	c.484-3_484-2insTTTTGTTTTTTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000379817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APTX	ENST00000379817.7	c.484-3_484-2insTTTTGTTTTTTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001195248.2	P1

Frequencies

GnomAD3 genomes AF: 0.0000695 AC: 1 AN: 14398 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: 0.000274 AC: 197 AN: 718818 Hom.: 4 Cov.: 10 AF XY: 0.000301 AC XY: 112 AN XY: 371572

Gnomad4 AFR exome AF: 0.000647

Gnomad4 AMR exome AF: 0.000524

Gnomad4 ASJ exome AF: 0.000372

Gnomad4 EAS exome AF: 0.00115

Gnomad4 SAS exome AF: 0.000718

Gnomad4 FIN exome AF: 0.000105

Gnomad4 NFE exome AF: 0.000179

Gnomad4 OTH exome AF: 0.000189

GnomAD4 genome AF: 0.0000695 AC: 1 AN: 14398 Hom.: 0 Cov.: 0 AF XY: 0.000150 AC XY: 1 AN XY: 6660

Gnomad4 AFR AF: 0.000194

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554664711; hg19: chr9-32986030;