rs397517041
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_004985.5(KRAS):c.454G>T(p.Val152Phe) 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. 9/15 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V152G) has been classified as Pathogenic.
Frequency
Consequence
NM_004985.5 missense
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 |
---|---|---|---|---|---|---|---|
KRAS | NM_004985.5 | c.454G>T | p.Val152Phe | missense_variant | 5/5 | ENST00000311936.8 | |
KRAS | NM_033360.4 | c.*8G>T | 3_prime_UTR_variant | 6/6 | ENST00000256078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRAS | ENST00000311936.8 | c.454G>T | p.Val152Phe | missense_variant | 5/5 | 1 | NM_004985.5 | P4 | |
KRAS | ENST00000256078.10 | c.*8G>T | 3_prime_UTR_variant | 6/6 | 1 | NM_033360.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 29
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Noonan syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 03, 2011 | The Val152Phe variant in KRAS has not been previously reported in the literature or been identified by our laboratory. However, a different amino acid change at this position, Val152Gly, has been reported as a de novo variant in an individu al with severe NS overlapping CS and CFC (Carta 2006). Val152 is conserved acros s evolutionarily distinct species and computational analyses (PolyPhen2, SIFT, A lignGVGD) predict that this variant will impact the normal function of KRAS. It should be noted that the sensitivity and specificity of these computational prog rams has not been determined by our laboratory. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at