rs1362209698
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_005343.4(HRAS):āc.452G>Cā(p.Gly151Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000274 in 1,460,260 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. 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. G151R) has been classified as Uncertain significance.
Frequency
Consequence
NM_005343.4 missense, splice_region
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.452G>C | p.Gly151Ala | missense_variant, splice_region_variant | 5/6 | ENST00000311189.8 | |
HRAS | NM_176795.5 | c.*21G>C | splice_region_variant, 3_prime_UTR_variant | 6/6 | ENST00000417302.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRAS | ENST00000311189.8 | c.452G>C | p.Gly151Ala | missense_variant, splice_region_variant | 5/6 | 1 | NM_005343.4 | P1 | |
HRAS | ENST00000417302.7 | c.*21G>C | splice_region_variant, 3_prime_UTR_variant | 6/6 | 5 | NM_176795.5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247598Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134498
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460260Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726478
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Costello syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 151 of the HRAS protein (p.Gly151Ala). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 462154). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at