rs587776594
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_001195248.2(APTX):c.841delT(p.Ser281LeufsTer8) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000687 in 1,455,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
APTX
NM_001195248.2 frameshift
NM_001195248.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.94
Publications
3 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 hypoalbuminemiaInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Genomics England PanelApp
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.183 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 9-32974490-GA-G is Pathogenic according to our data. Variant chr9-32974490-GA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 4427.Status of the report is no_assertion_criteria_provided, 0 stars.
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 | MANE Select | c.841delT | p.Ser281LeufsTer8 | frameshift | Exon 7 of 8 | NP_001182177.2 | Q7Z2E3-7 | ||
| APTX | c.841delT | p.Ser281LeufsTer8 | frameshift | Exon 7 of 8 | NP_001182178.1 | Q7Z2E3-7 | |||
| APTX | c.841delT | p.Ser281LeufsTer8 | frameshift | Exon 7 of 8 | NP_001355924.1 | Q7Z2E3-7 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| APTX | TSL:1 MANE Select | c.841delT | p.Ser281LeufsTer8 | frameshift | Exon 7 of 8 | ENSP00000369145.2 | Q7Z2E3-7 | ||
| APTX | TSL:1 | c.841delT | p.Ser281LeufsTer8 | frameshift | Exon 8 of 9 | ENSP00000369147.2 | Q7Z2E3-7 | ||
| APTX | TSL:1 | c.841delT | p.Ser281LeufsTer8 | frameshift | Exon 7 of 8 | ENSP00000419846.1 | Q7Z2E3-7 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455198Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724370 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1455198
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
724370
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33360
American (AMR)
AF:
AC:
0
AN:
44694
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26084
East Asian (EAS)
AF:
AC:
1
AN:
39574
South Asian (SAS)
AF:
AC:
0
AN:
86126
European-Finnish (FIN)
AF:
AC:
0
AN:
53002
Middle Eastern (MID)
AF:
AC:
0
AN:
5742
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1106416
Other (OTH)
AF:
AC:
0
AN:
60200
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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