chr12-25225624-T-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_ModeratePP5_Moderate
The NM_004985.5(KRAS):c.440A>G(p.Lys147Arg) variant causes a missense change involving the alteration of a 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K147E) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004985.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRAS | NM_033360.4 | c.440A>G | p.Lys147Arg | missense_variant | 4/6 | ENST00000256078.10 | |
KRAS | NM_004985.5 | c.440A>G | p.Lys147Arg | missense_variant | 4/5 | ENST00000311936.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRAS | ENST00000256078.10 | c.440A>G | p.Lys147Arg | missense_variant | 4/6 | 1 | NM_033360.4 | A1 | |
KRAS | ENST00000311936.8 | c.440A>G | p.Lys147Arg | missense_variant | 4/5 | 1 | NM_004985.5 | P4 | |
ENST00000620933.1 | n.522T>C | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Noonan syndrome 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg | Aug 01, 2017 | The missense variant c.440A>G, p.(Lys147Arg) in KRAS was identified in a girl with moderate ID, facial dysmorphism and normal growth. This variant could be excluded in her mother, while a paternal sample was not available. However, another missense mutation p.(Lys147Glu) at the same residue has been reported in a girl with Noonan syndrome and normal height, and the amino acid Lys147 has been shown to be one of the major ubiquitination sites of the KRAS protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at