22-50525775-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_001953.5(TYMP):c.1444C>T(p.Gln482Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,610,696 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q482Q) has been classified as Likely benign.
Frequency
Consequence
NM_001953.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYMP | NM_001953.5 | c.1444C>T | p.Gln482Ter | stop_gained | 10/10 | ENST00000252029.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYMP | ENST00000252029.8 | c.1444C>T | p.Gln482Ter | stop_gained | 10/10 | 1 | NM_001953.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152244Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.00000860 AC: 2AN: 232610Hom.: 0 AF XY: 0.00000776 AC XY: 1AN XY: 128940
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1458452Hom.: 0 Cov.: 38 AF XY: 0.00000276 AC XY: 2AN XY: 725530
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152244Hom.: 0 Cov.: 35 AF XY: 0.0000269 AC XY: 2AN XY: 74380
ClinVar
Submissions by phenotype
Mitochondrial DNA depletion syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Feb 02, 2022 | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with mitochondrial DNA depletion syndrome 1 (MNGIE type) (MIM#603041). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. Specifically, it truncates the last amino acid of the protein. (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 12 heterozygotes, 0 homozygotes). (SP) 0503 - The amino acid affected by the truncation is lowly conserved. (SB) 0705 - No comparable variants have previous evidence for pathogenicity. This variant truncates the last amino acid in the protein and no missense variant has been reported at this residue. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at