rs121909590
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_172351.3(CD46):c.175C>T(p.Arg59Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,684 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_172351.3 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CD46 | NM_172351.3 | c.175C>T | p.Arg59Ter | stop_gained | 2/13 | ENST00000367042.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD46 | ENST00000367042.6 | c.175C>T | p.Arg59Ter | stop_gained | 2/13 | 1 | NM_172351.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251414Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135890
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461546Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727108
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74322
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 21, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 17048). This variant is also known as R25Stop. This premature translational stop signal has been observed in individual(s) with hemolytic uremic syndrome (PMID: 16621965, 23780777, 34169201). This variant is present in population databases (rs121909590, gnomAD 0.009%). This sequence change creates a premature translational stop signal (p.Arg59*) in the CD46 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CD46 are known to be pathogenic (PMID: 16621965, 23431077). - |
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 27, 2022 | PP1, PS3_moderate, PS4_moderate, PVS1 - |
Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Aug 15, 2006 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at