chr22-50525872-GCCGCTGAGCGCGGGGCCGTC-G
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001953.5(TYMP):c.1327_1346del(p.Asp443ProfsTer?) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,439,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. D443D) has been classified as Likely benign.
Frequency
Consequence
NM_001953.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYMP | NM_001953.5 | c.1327_1346del | p.Asp443ProfsTer? | frameshift_variant | 10/10 | ENST00000252029.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYMP | ENST00000252029.8 | c.1327_1346del | p.Asp443ProfsTer? | frameshift_variant | 10/10 | 1 | NM_001953.5 | P2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 0.00000208 AC: 3AN: 1439240Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 714604
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Mitochondrial DNA depletion syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | GeneReviews | Jan 14, 2016 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | This sequence change results in a frameshift in the TYMP gene (p.Asp443Profs*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 40 amino acid(s) of the TYMP protein and extend the protein by an uncertain number of additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This frameshift has been observed in individual(s) with clinical features of mitochondrial neurogastrointestinal encephalomyopathy (PMID: 16198108). ClinVar contains an entry for this variant (Variation ID: 223086). This variant disrupts the C-terminus of the TYMP protein. Other variant(s) that disrupt this region (p.Ser471*) have been observed in individuals with TYMP-related conditions (PMID: 9924029, 17437622). This suggests that this may be a clinically significant region of the protein. 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