rs1057520098
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000355.4(TCN2):c.1099G>T(p.Gly367Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,876 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000355.4 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 |
---|---|---|---|---|---|---|---|
TCN2 | NM_000355.4 | c.1099G>T | p.Gly367Ter | stop_gained | 7/9 | ENST00000215838.8 | |
TCN2 | NM_001184726.2 | c.1018G>T | p.Gly340Ter | stop_gained | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCN2 | ENST00000215838.8 | c.1099G>T | p.Gly367Ter | stop_gained | 7/9 | 1 | NM_000355.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251452Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135912
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727232
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Oct 10, 2016 | - - |
Transcobalamin II deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 376962). This variant has not been reported in the literature in individuals affected with TCN2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Gly367*) in the TCN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCN2 are known to be pathogenic (PMID: 7980584, 20352340). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at