rs193921071

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_012424.6(RPS6KC1):ā€‹c.3163T>Cā€‹(p.Phe1055Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,390 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 Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

RPS6KC1
NM_012424.6 missense

Scores

10
7
2

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.86
Variant links:
Genes affected
RPS6KC1 (HGNC:10439): (ribosomal protein S6 kinase C1) Sphingosine kinase catalyzes the formation of sphingosine 1 phosphate, a lipid cellular messenger. The protein encoded by this gene can bind to sphingosine kinase and to phosphatidylinositol 3-phosphate, suggesting a role in sphingosine 1 phophate signaling. The encoded protein can also bind to peroxiredoxin-3 and may help transport it to mitochondria. [provided by RefSeq, Mar 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS6KC1NM_012424.6 linkuse as main transcriptc.3163T>C p.Phe1055Leu missense_variant 15/15 ENST00000366960.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS6KC1ENST00000366960.8 linkuse as main transcriptc.3163T>C p.Phe1055Leu missense_variant 15/151 NM_012424.6 P1Q96S38-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461390
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726988
show subpopulations
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria providedliterature onlyScience for Life laboratory, Karolinska Institutet-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.13
.;T;.;T;T;.
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
D;.;D;D;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.92
D;D;D;D;D;D
MetaSVM
Uncertain
0.0024
D
MutationAssessor
Uncertain
2.7
.;.;.;.;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-5.5
.;D;.;.;D;D
REVEL
Pathogenic
0.74
Sift
Uncertain
0.0010
.;D;.;.;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
.;D;.;D;D;.
Vest4
0.63
MutPred
0.85
.;.;.;.;Gain of catalytic residue at F1055 (P = 0.0617);.;
MVP
0.86
MPC
0.44
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.96
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs193921071; hg19: chr1-213445939; COSMIC: COSV65302116; API