chr8-42838315-G-A
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018105.3(THAP1):c.289C>T(p.Gln97Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
THAP1
NM_018105.3 stop_gained
NM_018105.3 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 1.65
Genes affected
THAP1 (HGNC:20856): (THAP domain containing 1) The protein encoded by this gene contains a THAP domain, a conserved DNA-binding domain. This protein colocalizes with the apoptosis response protein PAWR/PAR-4 in promyelocytic leukemia (PML) nuclear bodies, and functions as a proapoptotic factor that links PAWR to PML nuclear bodies. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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. There are 24 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-42838315-G-A is Pathogenic according to our data. Variant chr8-42838315-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 532262.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THAP1 | NM_018105.3 | c.289C>T | p.Gln97Ter | stop_gained | 3/3 | ENST00000254250.7 | |
THAP1 | NM_199003.2 | c.93C>T | p.His31= | synonymous_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THAP1 | ENST00000254250.7 | c.289C>T | p.Gln97Ter | stop_gained | 3/3 | 1 | NM_018105.3 | P1 | |
THAP1 | ENST00000345117.2 | c.93C>T | p.His31= | synonymous_variant | 2/2 | 1 | |||
THAP1 | ENST00000529779.1 | c.268-84C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Torsion dystonia 6 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 21, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 532262). This premature translational stop signal has been observed in individuals with dystonia (PMID: 24976531). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln97*) in the THAP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 117 amino acid(s) of the THAP1 protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
MutationTaster
Benign
D;D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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