rs367918552
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2
The ENST00000369535.5(NRAS):āc.504G>Cā(p.Met168Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M168K) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000369535.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NRAS | NM_002524.5 | c.504G>C | p.Met168Ile | missense_variant | 5/7 | ENST00000369535.5 | NP_002515.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NRAS | ENST00000369535.5 | c.504G>C | p.Met168Ile | missense_variant | 5/7 | 1 | NM_002524.5 | ENSP00000358548 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251472Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135908
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460936Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726846
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2017 | The M168I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M168I variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The M168I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Methionine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The NRAS gene has a very low rate of benign missense variants. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at