chr9-127825273-G-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001114753.3(ENG):c.774C>G(p.Tyr258Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Y258Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001114753.3 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.774C>G | p.Tyr258Ter | stop_gained | 6/15 | ENST00000373203.9 | |
ENG | NM_000118.4 | c.774C>G | p.Tyr258Ter | stop_gained | 6/14 | ||
ENG | NM_001278138.2 | c.228C>G | p.Tyr76Ter | stop_gained | 6/15 | ||
ENG | NM_001406715.1 | c.774C>G | p.Tyr258Ter | stop_gained | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.774C>G | p.Tyr258Ter | stop_gained | 6/15 | 1 | NM_001114753.3 | P2 | |
ENG | ENST00000344849.4 | c.774C>G | p.Tyr258Ter | stop_gained | 6/14 | 1 | A2 | ||
ENG | ENST00000480266.6 | c.228C>G | p.Tyr76Ter | stop_gained | 6/15 | 2 |
Frequencies
GnomAD3 genomes Cov.: 27
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 27
ClinVar
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Breda Genetics srl | Sep 10, 2019 | The variant c.774C>G (p.Tyr258*) creates a premature stop codon at amino acid position Tyr258 which is likely to result in a truncated protein or protein loss due to nonsense-mediated messenger decay (NMD). This variant has not been reported in dbSNP, gnomAD, 1000 Genomes, NHLI Exome Sequencing Project (ESP) or ClinVar. The variant c.774C>G (p.Tyr258*) is reported as pathogenic in the HHT Mutation Database (ENG), with 6 other pathogenic mutations (nonsense, frameshift) that fall on the same amminoacid position. Current data suggest that approximately two thirds of variants in the ENG gene are functionally null alleles (McDonald et al., 2000, PMID: 20301525). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at