rs397515524
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000370.3(TTPA):c.421G>T(p.Glu141Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,754 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. E141E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000370.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTPA | NM_000370.3 | c.421G>T | p.Glu141Ter | stop_gained | 3/5 | ENST00000260116.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTPA | ENST00000260116.5 | c.421G>T | p.Glu141Ter | stop_gained | 3/5 | 1 | NM_000370.3 | P1 | |
TTPA | ENST00000521138.1 | n.233-17432G>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251346Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135842
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461754Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727168
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with TTPA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu141*) in the TTPA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TTPA are known to be pathogenic (PMID: 9463307, 26068213). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at