chr9-32973570-ACAACGAAGGGGCAGCTT-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_001195248.2(APTX):βc.940_956delβ(p.Lys314SerfsTer2) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β ).
Frequency
Genomes: π 0.0000066 ( 0 hom., cov: 32)
Exomes π: 0.0000014 ( 0 hom. )
Consequence
APTX
NM_001195248.2 frameshift
NM_001195248.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.40
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0865 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 9-32973570-ACAACGAAGGGGCAGCTT-A is Pathogenic according to our data. Variant chr9-32973570-ACAACGAAGGGGCAGCTT-A is described in ClinVar as [Pathogenic]. Clinvar id is 870836.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-32973570-ACAACGAAGGGGCAGCTT-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APTX | NM_001195248.2 | c.940_956del | p.Lys314SerfsTer2 | frameshift_variant | 8/8 | ENST00000379817.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APTX | ENST00000379817.7 | c.940_956del | p.Lys314SerfsTer2 | frameshift_variant | 8/8 | 1 | NM_001195248.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461884Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727244
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74268
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2018 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at