rs1554884794
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_005343.4(HRAS):c.383G>T(p.Arg128Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R128P) has been classified as Uncertain significance.
Frequency
Consequence
NM_005343.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRAS | NM_005343.4 | c.383G>T | p.Arg128Leu | missense_variant | 4/6 | ENST00000311189.8 | |
HRAS | NM_176795.5 | c.383G>T | p.Arg128Leu | missense_variant | 4/6 | ENST00000417302.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRAS | ENST00000311189.8 | c.383G>T | p.Arg128Leu | missense_variant | 4/6 | 1 | NM_005343.4 | P1 | |
HRAS | ENST00000417302.7 | c.383G>T | p.Arg128Leu | missense_variant | 4/6 | 5 | NM_176795.5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461486Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727068
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Costello syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HRAS protein function. This variant has not been reported in the literature in individuals with HRAS-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 128 of the HRAS protein (p.Arg128Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.