rs199901350
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM5BS1_Supporting
The ENST00000252029.8(TYMP):c.401C>T(p.Ala134Val) variant causes a missense change. The variant allele was found at a frequency of 0.000351 in 1,613,030 control chromosomes in the GnomAD database, including 2 homozygotes. 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. A134E) has been classified as Pathogenic.
Frequency
Consequence
ENST00000252029.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TYMP | NM_001953.5 | c.401C>T | p.Ala134Val | missense_variant | 3/10 | ENST00000252029.8 | NP_001944.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TYMP | ENST00000252029.8 | c.401C>T | p.Ala134Val | missense_variant | 3/10 | 1 | NM_001953.5 | ENSP00000252029 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000401 AC: 61AN: 152164Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000399 AC: 100AN: 250314Hom.: 0 AF XY: 0.000346 AC XY: 47AN XY: 135708
GnomAD4 exome AF: 0.000346 AC: 505AN: 1460866Hom.: 1 Cov.: 32 AF XY: 0.000333 AC XY: 242AN XY: 726762
GnomAD4 genome AF: 0.000401 AC: 61AN: 152164Hom.: 1 Cov.: 33 AF XY: 0.000390 AC XY: 29AN XY: 74330
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 15, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 27, 2020 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 23, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 134 of the TYMP protein (p.Ala134Val). This variant is present in population databases (rs199901350, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with TYMP-related conditions. ClinVar contains an entry for this variant (Variation ID: 215330). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Mitochondrial DNA depletion syndrome 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 11, 2021 | - - |
Mitochondrial neurogastrointestinal encephalomyopathy Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at