The RAC1 NM_006908.5:c.85C>T (NP_008839.2:p.(Pro29Ser)) missense variant has previously been reported in somatic cancers (COSMIC; COSV61821563, n = 178 times), and lies in a statistically significant hotspot (cancerhotspots.org). Experimental evidence: Independent biochemical, cellular, and in vivo assays consistently show RAC1 p.Pro29Ser activation, including significantly increased GDP-to-GTP exchange and enhanced tumor growth or drug resistance. Based on available guidelines, this variant is considered to be a Variant of Uncertain Significance (VUS).
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.RAC1 encodes a small GTPase that helps regulate cell growth, cell shape and movement, adhesion, differentiation, and signaling pathways involved in inflammation and the cell cycle. Changes that increase RAC1 activity are associated with cancer development and progression, especially melanoma, and can contribute to metastasis and resistance to treatment. An alternatively spliced, continuously active form called RAC1B has also been identified in colon and lung cancer.
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
Met, strong: independent biochemical, cellular, and in vivo assays consistently show RAC1 p.Pro29Ser activation, including significantly increased GDP-to-GTP exchange and enhanced tumor growth or drug resistance.
Met at supporting strength: the variant is absent from all reported gnomAD datasets, giving observed frequency 0 versus the <=0.0001 PM2 threshold.
No benign criterion marked as applied in the recorded assessment.
VUS: PS3 (strong) plus PM2 (supporting) do not meet a generic ACMG/AMP 2015 pathogenic, likely pathogenic, benign, or likely benign combination.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1 allele counts were not recorded for this variant.
Absent from gnomAD v2.1.
Not available in gnomAD-Canada v1.0.
Recorded REVEL score: 0.585. Refer to the recorded PP3/BP4 rationale for interpretation.
A ClinVar laboratory submission summary was not recorded.
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Gain-of-function; curated oncogenicity label: Oncogenic.
This variant has previously been reported in somatic cancers (COSMIC; COSV61821563, n = 178 times).
This variant lies in a statistically significant hotspot.
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 15 not met · 7 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
For RAC1 p.Pro29Ser, the codon/residue evidence supports recurrent somatic oncogenic activity but does not establish PS1 or PM5 under the germline ACMG/AMP definitions.
PM1 is not met because the generic no-benign-variation domain requirement is not established and the supplied somatic hotspot cannot be used through a VCEP-specific route when no RAC1 VCEP exists.
PP2 and BP1 remain not assessed because the required gene-level missense and truncating disease-mechanism evidence is unavailable.
Variant-specific biochemical, cellular and in vivo studies consistently support RAC1 p.Pro29Ser gain of function and support PS3 at strong strength; BS3 is not met.
No criterion in this group is met under generic ACMG/AMP rules. The literature supports recurrent somatic RAC1 P29S in melanoma, but does not establish germline PS4, PP4, BP5, PP5, or BP6 evidence for this case.
No criteria match.
PS3 is met at strong strength. Four variant-specific publications directly evaluated RAC1 p.Pro29Ser (NM_006908.5:c.85C>T) using complementary, controlled functional systems. Recombinant-protein assays showed significantly increased spontaneous GDP-to-GTP exchange and increased PAK1 effector binding while retaining GTP hydrolysis (PMID:23284172). Independent biochemical assays found approximately 4.5- to 9-fold greater PAK1-PBD binding, increased MLK3 binding and enhanced ERK phosphorylation; cell-based assays showed increased membrane ruffling, proliferation and migration (PMID:22842228). Additional isogenic melanoma models demonstrated higher active RAC1, reduced inhibitor sensitivity and reduced apoptosis, with reduced RAF-inhibitor effects on tumor growth in vivo (PMID:25056119). These concordant biochemical, cellular and in vivo results directly support a damaging gain-of-function effect for the variant. The evidence satisfies the ACMG/AMP definition of a well-established functional study supportive of a damaging effect; no stronger calibration rule or validated clinical-laboratory assay threshold was supplied in the governing rules, so the original PS3 strong designation is retained.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
PM2 is met at supporting strength. RAC1 NM_006908.5:c.85C>T (p.Pro29Ser) is absent from gnomAD v2.1, gnomAD v4.1, gnomAD v2.1 non-cancer, and gnomAD v3.1 non-cancer. The default all-comers sources apply because no governing VCEP specifies an alternative source, and the variant's observed frequency is therefore 0 in each reported population dataset; this is <=0.0001, the supplied generic SVI supporting threshold. The variant is a single-nucleotide substitution, so the indel calling caveat does not apply.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
The variant is RAC1 p.Pro29Ser (c.85C>T), and the literature documents this exact amino-acid change repeatedly as a recurrent somatic melanoma gain-of-function mutation. However, the generic PS1 rule requires a previously established pathogenic variant, and these sources establish somatic oncogenic activity rather than a pathogenic germline variant for the case's disease context; ClinVar contains no exact record. Therefore PS1 is not met.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
PS2 is not met. The criterion requires a de novo occurrence of the variant in a patient with the disease, with both maternity and paternity confirmed, and no family history. No such observation exists for RAC1 NM_006908.5:c.85C>T (p.Pro29Ser): the variant is absent from ClinVar, and none of the five reviewed publications reports a germline proband, trio testing, parental confirmation of maternity or paternity, or a family history. The literature instead characterises c.85C>T as a UV-signature somatic missense hotspot of melanoma. In the exome-sequencing cohort of PMID:22842228 the mutation was somatic in every case for which matched normal DNA was available, and it was absent from dbSNP, 1000 Genomes, 2,577 germline exomes and 2,596 individuals from 57 populations; PMID:25056119 independently states that P29S has not been detected as a germline mutation in 1000 Genomes or among over 2,500 germline exomes. With no affected proband, no parental testing and affirmative evidence that this variant arises somatically rather than being transmitted or arising de novo in the germline, the evidentiary predicate of PS2 is unmet.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history. ... Confirmation of paternity only is insufficient. Egg donation, surrogate motherhood, errors in embryo transfer, etc. can contribute to non-maternity.
Rule basis is acmg_2015: "The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls." Note 1: "Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0." PMID:22842228 reports RAC1 P29S in 7/147 melanomas and 20/217 sun-exposed melanomas, with absence from 2,577 germline exomes and 2,596 individuals from 57 populations; PMID:25056119 reports approximately 4%-9% of melanomas and absence as a germline variant in cited population datasets. Using the expanded cohort and reported population comparison, the case frequency is 20/217 = 9.22% versus 0/2,596 controls; the uncorrected OR is infinite because no controls carried the variant, and the Haldane-Anscombe corrected OR is 539.0 (95% CI 32.5-8,945.8). These are somatic melanoma observations compared with population germline datasets, not a germline case-control study for the patient's disease, and no affected-patient phenotype cohort or matched unaffected control counts suitable for the ACMG PS4 comparison are established. Therefore the criterion is not met; the available cancer-frequency observations cannot be used as germline PS4 evidence.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
RAC1 p.Pro29Ser lies in the switch I region, described in PMID:22842228 as a critical functional region, and is a recurrent somatic melanoma hotspot in PMID:25056119 and Cancer Hotspots. Under the governing instructions, a somatic cancer hotspot cannot count for PM1 unless a VCEP names that source or hotspot route; RAC1 has no VCEP. The generic domain route also requires a critical and well-established functional domain without benign variation, and the available evidence does not establish the complete switch I domain as meeting the no-benign-variation requirement. Therefore PM1 is not met.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
No different missense substitution at RAC1 residue Pro29 is documented in the supplied evidence as determined pathogenic. The available papers concern the same p.Pro29Ser substitution, while the exact variant is absent from ClinVar and the PM5 candidate artifact contains no confirmed same-residue pathogenic comparator. Therefore PM5 is not met.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
PM6 is not met. PM6 covers an assumed de novo occurrence for which maternity and paternity have not been confirmed, so it still presumes a reported de novo event in a patient. No assumed or unconfirmed de novo occurrence of RAC1 NM_006908.5:c.85C>T (p.Pro29Ser) is described in any of the five reviewed publications or in ClinVar, where the variant is absent. The variant is instead documented as a recurrent somatic, UV-signature melanoma hotspot: somatic in all matched tumour-normal cases and undetected across more than 2,500 germline exomes in PMID:22842228, and explicitly described in PMID:25056119 as not detected as a germline mutation. There is therefore no de novo assertion, confirmed or assumed, to which PM6 could attach.
Assumed de novo, but without confirmation of paternity and maternity.
The variant is a missense substitution, NM_006908.5:c.85C>T (p.Pro29Ser), so the governing generic rule selects the REVEL path only; SpliceAI and BayesDel are not used for PP3 in this situation. REVEL is 0.585, below the published generic PP3 supporting threshold of >=0.644 (ClinGen SVI calibration, Pejaver et al. 2022, PMID:36413997), so multiple computational evidence supporting a deleterious effect are not established and PP3 is not met.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
Rule basis is acmg_2015: "Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology." The supplied case evidence contains no patient phenotype, family history, or disease-specific clinical description for a germline RAC1-associated disorder. The melanoma papers describe somatic RAC1 P29S in tumors and functional oncogenic effects, not a highly specific patient phenotype attributable to a single germline etiology. PP4 is therefore not met.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
Rule basis is acmg_2015: "Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation." ClinVar has no exact result for NM_006908.5:c.85C>T and no expert-panel classification. OncoKB labels the somatic variant Oncogenic, but this is not an exact-variant ClinVar expert-panel Pathogenic/Likely pathogenic classification and its underlying literature is independently available. PP5 is not met.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
BA1 is not met. RAC1 NM_006908.5:c.85C>T (p.Pro29Ser) is absent from gnomAD v2.1 and gnomAD v4.1, so no filtering allele frequency or grpmax FAF is available and the generic BA1 threshold of >=0.05 is not reached. The variant is a single-nucleotide substitution, so the indel calling caveat does not apply. Although the variant is a recurrent somatic RAC1 melanoma mutation, that observation does not establish a benign population-frequency criterion.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
BS1 is not met on the available population data. The variant is absent from gnomAD v2.1 and gnomAD v4.1, so the required filtering allele frequency (grpmax FAF) is unavailable and is not >=0.01, the generic SVI default. No ancestry-specific elevated frequency is present from which to infer a founder or reduced-penetrance exception, and no maximum-credible-allele-frequency calculation is needed for an absent variant.
Allele frequency is greater than expected for the disorder.
BS3 is not met. The reviewed variant-specific studies do not show no damaging effect on RAC1 function or splicing; instead, they consistently demonstrate activation and oncogenic functional effects for RAC1 p.Pro29Ser. No well-established benign functional or splicing assay result was identified among the reviewed sources, and the available evidence is directionally incompatible with BS3.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
The variant is a missense substitution, NM_006908.5:c.85C>T (p.Pro29Ser), so the governing generic rule selects the REVEL path only; the low SpliceAI score cannot substitute for a gray-zone REVEL result, and BayesDel is not usable without generic ACMG-strength calibration. REVEL is 0.585, above the published generic BP4 supporting threshold of <=0.29 (ClinGen SVI calibration, Pejaver et al. 2022, PMID:36413997), so computational evidence suggesting no impact is not established and BP4 is not met.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
Rule basis is acmg_2015: "Variant found in a case with an alternate molecular basis for disease." The evidence shows RAC1 P29S as a recurrent somatic melanoma mutation and reports other tumor alterations in some studies, but it does not document this variant in a clinical case with an alternate molecular basis for the disease being evaluated. No BP5-qualifying case evidence is available.
Variant found in a case with an alternate molecular basis for disease.
Rule basis is acmg_2015: "Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation." ClinVar has no exact result for NM_006908.5:c.85C>T and no expert-panel Benign/Likely benign classification. No reputable independent benign assertion meeting the required exact-variant expert-panel rule is present. BP6 is not met.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
The available evidence does not report an affected proband with a second pathogenic RAC1 allele, nor parent or offspring testing establishing phase. The available variant-specific publications describe somatic melanoma observations and functional studies, not recessive disease cases or a pathogenic variant in trans. Therefore, the PM3 requirement cannot be assessed.
For recessive disorders, detected in trans with a pathogenic variant. ... This requires testing of parents (or offspring) to determine phase.
PP1 cannot be assessed. The criterion requires co-segregation of the variant with disease in multiple affected members of a family. No pedigree, no affected relative, and no genotyped family member is described for this variant in ClinVar or in any of the five reviewed publications. All reviewed sources are somatic melanoma case series, cell-line panels, or functional/biochemical studies; none reports family recruitment, affected versus unaffected relative genotyping, or LOD-type segregation analysis. There is consequently no segregation count either way, and PP1 is left unassessed rather than not met.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease. ... May be used as stronger evidence with increasing segregation data.
The supplied evidence establishes that RAC1 p.Pro29Ser is absent from gnomAD, but PP2 requires gene-level evidence that RAC1 has a low rate of benign missense variation and that missense variants are a common disease mechanism. No gene-level benign-missense rate or disease-mechanism dataset sufficient for both requirements is supplied.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
BS2 cannot be assessed. The case bundle contains no observation of this variant in a healthy adult individual, no homozygote or hemizygote count, and no disease-specific inheritance, age-of-onset, penetrance, or healthy-control phenotype information. Population absence in gnomAD is not evidence that a healthy adult carried the variant.
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
BS4 cannot be assessed. The criterion requires lack of segregation of the variant among affected members of a family, which presupposes an ascertained family with multiple affected individuals and genotyping of both affected and unaffected members. No family is described for this variant: ClinVar has no record, and none of the five reviewed publications reports a pedigree, affected relative genotypes, or a non-segregation analysis. The observation that c.85C>T is a recurrent somatic melanoma hotspot in unrelated tumours is a statement about tumour genomes, not about segregation within a family, so it neither supports nor refutes BS4. Because no informative family exists, lack of segregation cannot be demonstrated.
Lack of segregation in affected members of a family.
The supplied evidence does not establish that RAC1-related disease is caused primarily by truncating variants. The available RAC1 literature for p.Pro29Ser is predominantly somatic cancer literature and does not provide the required gene-level disease-variant spectrum for applying BP1.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
The available evidence does not report this variant with a pathogenic variant in trans in an affected dominant-disorder proband, or in cis with a pathogenic variant in any inheritance pattern. No parent or offspring phase testing and no relevant clinical allelic observation are available. Therefore, BP2 cannot be assessed.
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
PVS1 (ClinGen SVI PVS1 recommendations, PMC6185798, pvs1_generic_framework) applies only to null variant classes — nonsense, frameshift, canonical ±1/2 splice-consensus, translation-initiation-codon loss, and stop-loss variants — each expected to trigger nonsense-mediated decay or otherwise abolish normal protein function. NM_006908.5:c.85C>T in RAC1 is a missense substitution predicted to produce NP_008839.2:p.(Pro29Ser). As a result, no null-variant mechanism (nonsense-mediated decay, truncation, or canonical splice disruption) is triggered by this variant class, so PVS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PVS1 for RAC1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_null_variant_class
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_006908.5:c.85C>T in RAC1 is a missense substitution predicted to produce NP_008839.2:p.(Pro29Ser). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM4 for RAC1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_stop_loss_or_nonrepeat_indel
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_006908.5:c.85C>T in RAC1 is a missense substitution predicted to produce NP_008839.2:p.(Pro29Ser). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP3 for RAC1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_repeat_region_indel
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_006908.5:c.85C>T in RAC1 is a missense substitution predicted to produce NP_008839.2:p.(Pro29Ser). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for RAC1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
Every interpreted variant in RAC1, mapped onto the exon structure of NM_006908.5. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
Absent from gnomAD v4.1.
Absent from gnomAD v2.1.
Not available in gnomAD-Canada v1.0.
The variant is a missense substitution, NM_006908.5:c.85C>T (p.Pro29Ser), so the governing generic rule selects the REVEL path only; SpliceAI and BayesDel are not used for PP3 in this situation. REVEL is 0.585, below the published generic PP3 supporting threshold of >=0.644 (ClinGen SVI calibration, Pejaver et al. 2022, PMID:36413997), so multiple computational evidence supporting a deleterious effect are not established and PP3 is not met.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
The variant is a missense substitution, NM_006908.5:c.85C>T (p.Pro29Ser), so the governing generic rule selects the REVEL path only; the low SpliceAI score cannot substitute for a gray-zone REVEL result, and BayesDel is not usable without generic ACMG-strength calibration. REVEL is 0.585, above the published generic BP4 supporting threshold of <=0.29 (ClinGen SVI calibration, Pejaver et al. 2022, PMID:36413997), so computational evidence suggesting no impact is not established and BP4 is not met.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_006908.5:c.85C>T in RAC1 is a missense substitution predicted to produce NP_008839.2:p.(Pro29Ser). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for RAC1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.585. BayesDel score = 9.90479e-05.
5 paper records listed. 4 cited in the classification.
In addition to known recurrent mutations in BRAF and NRAS, we found a previously unidentified recurrent mutation in RAC1 (ras-related C3 botulinum toxin substrate 1), a C>T transition (CCT>TCT) resulting in a p.Pro29Ser substitution (Supplementary Fig. 1b; designated here RAC1P29S), in 7 of the 147 tumors. These pulldown experiments showed that RAC1P29S is a gain-of-function mutation.
Location Results, “Recurrent mutations” and “RAC1P29S mutations”; “Analyses of RAC1P29S effector binding activity”; “Functional analyses of RAC1P29S in normal and malignant cells”
Context Exome sequencing of 147 melanomas; expanded melanoma cohort and cell-line testing; matched tumor-normal somatic testing; structural analysis; in vitro effector-binding assays; and expression studies in melanocytes and COS-7 cells.
We found that RAC1P29S is a spontaneously activating GTPase with significantly increased inherent GDP→GTP nucleotide exchange compared with that of RAC1WT.
Location Results, “RAC1P29S Displays a Fast-Cycling Phenotype”; Discussion
Context In vitro recombinant RAC1 nucleotide-exchange assays, PAK1 pull-down assays, GTP hydrolysis assays, structural comparisons, and cell-expression/microscopy experiments.
Recently, two large-scale whole exome sequencing (WES) studies have revealed that in addition to recurrent mutations in BRAF and NRAS, the next most frequently observed somatic protein-coding hotspot mutation in melanoma of cutaneous origin is the RAC1 c.85C>T single-nucleotide variant (SNV) encoding the P29S amino acid change found in approximately 4% to 9% of melanomas (10, 11).
Location Introduction; Results, “RAC1 P29S Mutant Melanoma Cell Lines Have Higher Levels of Activated RAC1 and Display Differential Sensitivity to RAF and MEK Inhibitors”
Context Melanoma cell-line genotyping; RAC1 activation and inhibitor-response assays; isogenic overexpression models; xenograft experiments; and a clinical cohort of 45 treated patients.
When mutant RAC1P29S is introduced into normal melanocytes, it increases membrane ruffling and promotes proliferation and migration.
Location Abstract and main text discussion of RAC1P29S function
Context Review of approximately 4,600 sun-exposed melanomas and of biochemical, melanocyte ectopic-expression, knockdown and drug-response experiments in RAC1P29S melanoma models.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
Absent from gnomAD v4.1.
Absent from gnomAD v2.1.
Not available in gnomAD-Canada v1.0.
This variant is absent from ClinVar.
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.585. BayesDel score = 9.90479e-05.
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Gain-of-function; curated oncogenicity label: Oncogenic.
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV61821563, n = 178 times).
This variant lies in a statistically significant hotspot.