chr9-32986032-T-TAAAAAAAAACA

Variant names:

• chr9-32986032-T-TAAAAAAAAACA
• rs1554664711
• NM_001195248.2:c.484-3_484-2insTGTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001195248.2(APTX):​c.484-3_484-2insTGTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00059 (3 hom.)
• Consequence: APTX NM_001195248.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter 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 -10 ACMG points.

• BP6: Variant 9-32986032-T-TAAAAAAAAACA is Benign according to our data. Variant chr9-32986032-T-TAAAAAAAAACA is described in ClinVar as [Likely_benign]. Clinvar id is 2693722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000586 (421/718738) while in subpopulation EAS AF= 0.00196 (48/24444). AF 95% confidence interval is 0.00152. There are 3 homozygotes in gnomad4_exome. There are 224 alleles in male gnomad4_exome subpopulation. Median coverage is 10. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000278 AC: 4 AN: 14364 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: 0.00258

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000329

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000586 AC: 421 AN: 718738 Hom.: 3 Cov.: 10 AF XY: 0.000603 AC XY: 224 AN XY: 371534

Gnomad4 AFR exome AF: 0.00110

Gnomad4 AMR exome AF: 0.00109

Gnomad4 ASJ exome AF: 0.000434

Gnomad4 EAS exome AF: 0.00196

Gnomad4 SAS exome AF: 0.00161

Gnomad4 FIN exome AF: 0.000457

Gnomad4 NFE exome AF: 0.000391

Gnomad4 OTH exome AF: 0.000629

GnomAD4 genome AF: 0.000279 AC: 4 AN: 14360 Hom.: 0 Cov.: 0 AF XY: 0.000451 AC XY: 3 AN XY: 6650

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00260

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000330

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 24, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;