rs1554599707
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_018105.3(THAP1):c.161G>C(p.Cys54Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C54F) has been classified as Likely pathogenic.
Frequency
Consequence
NM_018105.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THAP1 | NM_018105.3 | c.161G>C | p.Cys54Ser | missense_variant | 2/3 | ENST00000254250.7 | |
THAP1 | NM_199003.2 | c.72-956G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THAP1 | ENST00000254250.7 | c.161G>C | p.Cys54Ser | missense_variant | 2/3 | 1 | NM_018105.3 | P1 | |
THAP1 | ENST00000345117.2 | c.72-956G>C | intron_variant | 1 | |||||
THAP1 | ENST00000529779.1 | c.161G>C | p.Cys54Ser | missense_variant | 2/3 | 5 | |||
THAP1 | ENST00000532093.1 | n.391G>C | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461778Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727186
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Torsion dystonia 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2016 | This sequence change replaces cysteine with serine at codon 54 of the THAP1 protein (p.Cys54Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a THAP1-related disease.  However, two different substitutions of this amino acid (p.Cys54Phe and p.Cys54Tyr) have been reported in individuals with dystonia (PMIDs: 21800139, 20865765). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at