Variant 1-213071024-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_012424.6(RPS6KC1):c.124C>A(p.Pro42Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00296 in 1,541,346 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 7 hom. )

Consequence

RPS6KC1
NM_012424.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.08

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]

RPS6KC1 links:

RPS6KC1 (HGNC:):

RPS6KC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0115995705).

BP6

Variant 1-213071024-C-A is Benign according to our data. Variant chr1-213071024-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1159111.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KC1	NM_012424.6 linkuse as main transcript	c.124C>A	p.Pro42Thr	missense_variant	2/15	ENST00000366960.8	NP_036556.2	Q96S38-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KC1	ENST00000366960.8 linkuse as main transcript	c.124C>A	p.Pro42Thr	missense_variant	2/15	1	NM_012424.6	ENSP00000355927.3		Q96S38-1

Frequencies

GnomAD3 genomes

AF:

0.00243

AC:

370

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00293

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00407

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00263

AC:

573

AN:

218054

Hom.:

AF XY:

0.00260

AC XY:

308

AN XY:

118534

show subpopulations

Gnomad AFR exome

AF:

0.000642

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.000642

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.00453

Gnomad OTH exome

AF:

0.00235

GnomAD4 exome

AF:

0.00302

AC:

4200

AN:

1389170

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

2014

AN XY:

692878

show subpopulations

Gnomad4 AFR exome

AF:

0.000621

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.000595

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00220

Gnomad4 NFE exome

AF:

0.00360

Gnomad4 OTH exome

AF:

0.00281

GnomAD4 genome

AF:

0.00243

AC:

370

AN:

152176

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00293

Gnomad4 NFE

AF:

0.00407

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.00261

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00287

AC:

348

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.041

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.7

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.30

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.56

MVP

0.64

MPC

0.21

ClinPred

0.036

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.52

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over