rs121913038
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_001953.5(TYMP):c.457G>A(p.Gly153Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,838 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. G153G) has been classified as Likely benign.
Frequency
Consequence
NM_001953.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYMP | NM_001953.5 | c.457G>A | p.Gly153Ser | missense_variant | 4/10 | ENST00000252029.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYMP | ENST00000252029.8 | c.457G>A | p.Gly153Ser | missense_variant | 4/10 | 1 | NM_001953.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251142Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135826
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461644Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727126
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
Mitochondrial DNA depletion syndrome 1 Pathogenic:4
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 29, 1999 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 29, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 09, 2021 | - - |
Pathogenic, no assertion criteria provided | literature only | GeneReviews | Jan 14, 2016 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 12, 2023 | PP3, PP4, PM2, PM3_strong, PS4_moderate - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 153 of the TYMP protein (p.Gly153Ser). This variant is present in population databases (rs121913038, gnomAD 0.007%). This missense change has been observed in individual(s) with mitochondrial neurogastrointestinal encephalomyopathy (PMID: 9924029, 16178026). ClinVar contains an entry for this variant (Variation ID: 16660). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TYMP protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. - |
Mitochondrial neurogastrointestinal encephalomyopathy Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 23, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at