dbSNP rs774887864: RPS6KL1:p.Glu501Gln (chr14-74907473-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031464.5(RPS6KL1):c.1501G>C(p.Glu501Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,588,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

RPS6KL1
NM_031464.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.92

Variant links:

Genes affected

RPS6KL1 (HGNC:20222): (ribosomal protein S6 kinase like 1) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be located in ribosome. [provided by Alliance of Genome Resources, Apr 2022]

RPS6KL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2190749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KL1	NM_031464.5 link	c.1501G>C	p.Glu501Gln	missense_variant	Exon 11 of 12	ENST00000557413.6	NP_113652.2	Q9Y6S9-1B4DSP6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KL1	ENST00000557413.6 link	c.1501G>C	p.Glu501Gln	missense_variant	Exon 11 of 12	5	NM_031464.5	ENSP00000450567.1		Q9Y6S9-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1436538

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711814

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:

9.09e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0046

T;T;.;.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.71

T;.;T;T;.

M_CAP

Benign

0.0086

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;.;.;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.1

.;N;D;N;N

REVEL

Benign

0.041

Sift

Uncertain

0.014

.;D;D;T;D

Sift4G

Uncertain

0.060

T;T;D;T;T

Polyphen

0.97

D;D;.;.;D

Vest4

0.37

MutPred

0.28

Loss of phosphorylation at S504 (P = 0.1373);Loss of phosphorylation at S504 (P = 0.1373);.;.;Loss of phosphorylation at S504 (P = 0.1373);

MVP

0.43

MPC

0.60

ClinPred

0.78

GERP RS

1.8

Varity_R

0.087

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over