rs764960797
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_194454.3(KRIT1):c.880C>T(p.Arg294Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,802 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_194454.3 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 |
---|---|---|---|---|---|---|---|
KRIT1 | NM_194454.3 | c.880C>T | p.Arg294Ter | stop_gained | 10/19 | ENST00000394505.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRIT1 | ENST00000394505.7 | c.880C>T | p.Arg294Ter | stop_gained | 10/19 | 1 | NM_194454.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251360Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135878
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460802Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726816
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30161288, 31254430, 34426522, 31589614, 24466005, 23595507) - |
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 30, 2018 | - - |
Cerebral cavernous malformation Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 20, 2021 | This variant is present in population databases (rs764960797, ExAC 0.009%). This sequence change creates a premature translational stop signal (p.Arg294*) in the KRIT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KRIT1 are known to be pathogenic (PMID: 10508515, 11222804, 12404106, 24689081). This premature translational stop signal has been observed in individual(s) with cerebral cavernous malformations (PMID: 23595507, 31254430). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 590759). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at