chr1-155900444-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_006912.6(RIT1):c.604A>T(p.Ser202Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,878 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: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
RIT1
NM_006912.6 missense
NM_006912.6 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 4.61
Genes affected
RIT1 (HGNC:10023): (Ras like without CAAX 1) This gene encodes a member of a subfamily of Ras-related GTPases. The encoded protein is involved in regulating p38 MAPK-dependent signaling cascades related to cellular stress. This protein also cooperates with nerve growth factor to promote neuronal development and regeneration. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM1
?
In a chain GTP-binding protein Rit1 (size 218) in uniprot entity RIT1_HUMAN there are 53 pathogenic changes around while only 9 benign (85%) in NM_006912.6
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.23878428).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIT1 | NM_006912.6 | c.604A>T | p.Ser202Cys | missense_variant | 6/6 | ENST00000368323.8 | |
RIT1 | NM_001256821.2 | c.655A>T | p.Ser219Cys | missense_variant | 6/6 | ||
RIT1 | NM_001256820.2 | c.496A>T | p.Ser166Cys | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIT1 | ENST00000368323.8 | c.604A>T | p.Ser202Cys | missense_variant | 6/6 | 1 | NM_006912.6 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727240
GnomAD4 exome
AF:
AC:
5
AN:
1461878
Hom.:
Cov.:
31
AF XY:
AC XY:
4
AN XY:
727240
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 13, 2015 | The p.Ser219Cys variant in RIT1 has been identified by our laboratory in 1 fetus with a cystic hygroma and hydrops, which was inherited from a parent of unknown clinical status. It was not observed in large population studies. Computational prediction tools and conservation analyses suggest that the p.Ser219Cyc variant may impact the protein, though this information is not predictive enough to det ermine pathogenicity. In summary, the clinical significance of the p.Ser219Cys v ariant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
D;T;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of phosphorylation at S202 (P = 0.0166);.;.;
MVP
MPC
0.78
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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