9-32986032-T-TAAAAAAAAACAA

Position:

• chr9-32986032-T-TAAAAAAAAACAA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001195248.2(APTX):​c.484-3_484-2insTTGTTTTTTTTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0028 (17 hom.)
  • Failed GnomAD Quality Control
• Consequence: APTX NM_001195248.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• 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 Benign. Variant got -9 ACMG points.

• BP6: Variant 9-32986032-T-TAAAAAAAAACAA is Benign according to our data. Variant chr9-32986032-T-TAAAAAAAAACAA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 446857.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00281 (2015/717624) while in subpopulation EAS AF= 0.0149 (361/24302). AF 95% confidence interval is 0.0136. There are 17 homozygotes in gnomad4_exome. There are 1122 alleles in male gnomad4_exome subpopulation. Median coverage is 10. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APTX	NM_001195248.2	c.484-3_484-2insTTGTTTTTTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000379817.7	NP_001182177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000379817.7	c.484-3_484-2insTTGTTTTTTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001195248.2	ENSP00000369145	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 18 AN: 14344 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000777

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000840

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00429

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00180

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00281 AC: 2015 AN: 717624 Hom.: 17 Cov.: 10 AF XY: 0.00302 AC XY: 1122 AN XY: 370912

Gnomad4 AFR exome AF: 0.00532

Gnomad4 AMR exome AF: 0.00590

Gnomad4 ASJ exome AF: 0.00249

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.00725

Gnomad4 FIN exome AF: 0.000880

Gnomad4 NFE exome AF: 0.00175

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00126 AC: 18 AN: 14340 Hom.: 0 Cov.: 0 AF XY: 0.00181 AC XY: 12 AN XY: 6640

Gnomad4 AFR AF: 0.000774

Gnomad4 AMR AF: 0.000846

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00433

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00180

Gnomad4 NFE AF: 0.00165

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 11, 2017

- -

Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

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;