rs730880462
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_005343.4(HRAS):c.317C>T(p.Ser106Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,534 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. S106W) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRAS | NM_005343.4 | c.317C>T | p.Ser106Leu | missense_variant | 4/6 | ENST00000311189.8 | |
HRAS | NM_176795.5 | c.317C>T | p.Ser106Leu | missense_variant | 4/6 | ENST00000417302.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRAS | ENST00000311189.8 | c.317C>T | p.Ser106Leu | missense_variant | 4/6 | 1 | NM_005343.4 | P1 | |
HRAS | ENST00000417302.7 | c.317C>T | p.Ser106Leu | missense_variant | 4/6 | 5 | NM_176795.5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251380Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135904
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461534Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727084
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Costello syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 26, 2023 | ClinVar contains an entry for this variant (Variation ID: 409948). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. This variant is present in population databases (rs730880462, gnomAD 0.002%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 106 of the HRAS protein (p.Ser106Leu). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt HRAS function. 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