chr19-49635657-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006270.5(RRAS):c.576A>G(p.Lys192=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000076 in 1,316,390 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 (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000076 ( 0 hom. )
Consequence
RRAS
NM_006270.5 synonymous
NM_006270.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0990
Genes affected
RRAS (HGNC:10447): (RAS related) The protein encoded by this gene is a small GTPase involved in diverse processes including angiogenesis, vascular homeostasis and regeneration, cell adhesion, and neuronal axon guidance. Mutations in this gene are found in many invasive cancers. [provided by RefSeq, Jul 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RRAS | NM_006270.5 | c.576A>G | p.Lys192= | synonymous_variant | 6/6 | ENST00000246792.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RRAS | ENST00000246792.4 | c.576A>G | p.Lys192= | synonymous_variant | 6/6 | 1 | NM_006270.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
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31
GnomAD3 exomes AF: 0.00000554 AC: 1AN: 180512Hom.: 0 AF XY: 0.0000103 AC XY: 1AN XY: 97090
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GnomAD4 exome AF: 0.00000760 AC: 10AN: 1316390Hom.: 0 Cov.: 31 AF XY: 0.00000620 AC XY: 4AN XY: 645428
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GnomAD4 genome ? Cov.: 31
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Noonan syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 11, 2023 | This sequence change affects codon 192 of the RRAS mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RRAS protein. This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with RRAS-related conditions. 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
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at