rs1054084896
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001953.5(TYMP):c.112G>T(p.Glu38Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,728 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 (★★). Synonymous variant affecting the same amino acid position (i.e. E38E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001953.5 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 |
---|---|---|---|---|---|---|---|
TYMP | NM_001953.5 | c.112G>T | p.Glu38Ter | stop_gained | 2/10 | ENST00000252029.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYMP | ENST00000252029.8 | c.112G>T | p.Glu38Ter | stop_gained | 2/10 | 1 | NM_001953.5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248462Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135144
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460728Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726712
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Mitochondrial DNA depletion syndrome 1 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 06, 2023 | - - |
Pathogenic, no assertion criteria provided | literature only | GeneReviews | Jan 14, 2016 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | This sequence change creates a premature translational stop signal (p.Glu38*) in the TYMP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TYMP are known to be pathogenic (PMID: 9924029, 15781193). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with mitochondrial neurogastrointestinal encephalomyopathy (PMID: 20585803, 28764801). ClinVar contains an entry for this variant (Variation ID: 223014). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at