rs1057517423
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000360.4(TH):c.601C>T(p.Gln201Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,034 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000360.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TH | NM_000360.4 | c.601C>T | p.Gln201Ter | stop_gained | 5/13 | ENST00000352909.8 | |
TH | NM_199292.3 | c.694C>T | p.Gln232Ter | stop_gained | 6/14 | ||
TH | NM_199293.3 | c.682C>T | p.Gln228Ter | stop_gained | 6/14 | ||
TH | XM_011520335.3 | c.613C>T | p.Gln205Ter | stop_gained | 5/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TH | ENST00000352909.8 | c.601C>T | p.Gln201Ter | stop_gained | 5/13 | 1 | NM_000360.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000408 AC: 1AN: 245306Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133328
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459034Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 725672
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Autosomal recessive DOPA responsive dystonia Pathogenic:5
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 04, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2023 | This sequence change creates a premature translational stop signal (p.Gln232*) in the TH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TH are known to be pathogenic (PMID: 22264700, 24753243). This variant is present in population databases (no rsID available, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with tyrosine hydroxylase deficiency (PMID: 20823027, 22264700). ClinVar contains an entry for this variant (Variation ID: 371630). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 08, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 02, 2016 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Center for Molecular Medicine, Children’s Hospital of Fudan University | Feb 08, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at