rs2663698

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_005406.3(ROCK1):ā€‹c.3790T>Cā€‹(p.Cys1264Arg) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.00013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ROCK1
NM_005406.3 missense

Scores

13
3
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.25
Variant links:
Genes affected
ROCK1 (HGNC:10251): (Rho associated coiled-coil containing protein kinase 1) This gene encodes a protein serine/threonine kinase that is activated when bound to the GTP-bound form of Rho. The small GTPase Rho regulates formation of focal adhesions and stress fibers of fibroblasts, as well as adhesion and aggregation of platelets and lymphocytes by shuttling between the inactive GDP-bound form and the active GTP-bound form. Rho is also essential in cytokinesis and plays a role in transcriptional activation by serum response factor. This protein, a downstream effector of Rho, phosphorylates and activates LIM kinase, which in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. A pseudogene, related to this gene, is also located on chromosome 18. [provided by RefSeq, Aug 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.985

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ROCK1NM_005406.3 linkuse as main transcriptc.3790T>C p.Cys1264Arg missense_variant 31/33 ENST00000399799.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ROCK1ENST00000399799.3 linkuse as main transcriptc.3790T>C p.Cys1264Arg missense_variant 31/331 NM_005406.3 P1
ROCK1ENST00000578051.1 linkuse as main transcriptc.25T>C p.Cys9Arg missense_variant 1/22
ROCK1ENST00000635540.2 linkuse as main transcriptc.*425T>C 3_prime_UTR_variant, NMD_transcript_variant 32/345
ROCK1ENST00000584687.1 linkuse as main transcript downstream_gene_variant 4

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
18
AN:
147984
Hom.:
0
Cov.:
33
FAILED QC
Gnomad AFR
AF:
0.0000250
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000820
Gnomad SAS
AF:
0.000217
Gnomad FIN
AF:
0.000293
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000135
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1460936
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726782
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000128
AC:
19
AN:
148092
Hom.:
0
Cov.:
33
AF XY:
0.000166
AC XY:
12
AN XY:
72352
show subpopulations
Gnomad4 AFR
AF:
0.0000250
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00103
Gnomad4 SAS
AF:
0.000217
Gnomad4 FIN
AF:
0.000293
Gnomad4 NFE
AF:
0.000135
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000429
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.45
CADD
Pathogenic
32
DANN
Benign
0.93
DEOGEN2
Uncertain
0.48
T;.
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.75
T;T
M_CAP
Pathogenic
0.79
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Pathogenic
0.97
D
MutationAssessor
Uncertain
2.1
M;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.94
D
PROVEAN
Pathogenic
-9.8
D;.
REVEL
Pathogenic
0.94
Sift
Uncertain
0.0010
D;.
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;.
Vest4
0.91
MutPred
0.85
Gain of disorder (P = 0.0207);.;
MVP
0.98
MPC
4.9
ClinPred
1.0
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.96
gMVP
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2663698; hg19: chr18-18534807; COSMIC: COSV67695441; COSMIC: COSV67695441; API