rs1782949423
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM1PM2PP2PP3PP5
The NM_006908.5(RAC1):c.77A>G(p.Asn26Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,417,550 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
RAC1
NM_006908.5 missense
NM_006908.5 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 9.19
Publications
0 publications found
Genes affected
RAC1 (HGNC:9801): (Rac family small GTPase 1) The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
RAC1 Gene-Disease associations (from GenCC):
- intellectual disability, autosomal dominant 48Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Illumina, Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PM1
In a chain Ras-related C3 botulinum toxin substrate 1 (size 188) in uniprot entity RAC1_HUMAN there are 25 pathogenic changes around while only 1 benign (96%) in NM_006908.5
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the RAC1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 23 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 3.1347 (above the threshold of 3.09). Trascript score misZ: 3.9366 (above the threshold of 3.09). GenCC associations: The gene is linked to intellectual disability, autosomal dominant 48.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.799
PP5
Variant 7-6387253-A-G is Pathogenic according to our data. Variant chr7-6387253-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 986286.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Pathogenic=1}.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.05e-7 AC: 1AN: 1417550Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 706086 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1417550
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
706086
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
30006
American (AMR)
AF:
AC:
0
AN:
32784
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25124
East Asian (EAS)
AF:
AC:
0
AN:
37234
South Asian (SAS)
AF:
AC:
0
AN:
79830
European-Finnish (FIN)
AF:
AC:
0
AN:
53128
Middle Eastern (MID)
AF:
AC:
0
AN:
5676
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1095182
Other (OTH)
AF:
AC:
0
AN:
58586
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Mar 31, 2025
GeneDx
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Inborn genetic diseases Uncertain:1
Apr 09, 2018
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Gain of glycosylation at N26 (P = 0.0816);Gain of glycosylation at N26 (P = 0.0816);
MVP
MPC
2.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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