chr11-533535-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 6P and 4B. PM1PP3_StrongBS2
The NM_005343.4(HRAS):āc.368G>Cā(p.Arg123Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000421 in 1,613,718 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 Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R123C) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRAS | NM_005343.4 | c.368G>C | p.Arg123Pro | missense_variant | 4/6 | ENST00000311189.8 | |
HRAS | NM_176795.5 | c.368G>C | p.Arg123Pro | missense_variant | 4/6 | ENST00000417302.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRAS | ENST00000311189.8 | c.368G>C | p.Arg123Pro | missense_variant | 4/6 | 1 | NM_005343.4 | P1 | |
HRAS | ENST00000417302.7 | c.368G>C | p.Arg123Pro | missense_variant | 4/6 | 5 | NM_176795.5 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251332Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135904
GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461514Hom.: 0 Cov.: 35 AF XY: 0.0000495 AC XY: 36AN XY: 727080
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74352
ClinVar
Submissions by phenotype
Costello syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2023 | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 123 of the HRAS protein (p.Arg123Pro). This variant is present in population databases (rs730880464, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 180852). 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 expected to disrupt HRAS protein function with a positive predictive value of 95%. 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 19, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at