chr14-74907076-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031464.5(RPS6KL1):​c.1588G>T​(p.Val530Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RPS6KL1
NM_031464.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPS6KL1NM_031464.5 linkc.1588G>T p.Val530Phe missense_variant Exon 12 of 12 ENST00000557413.6 NP_113652.2 Q9Y6S9-1B4DSP6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS6KL1ENST00000557413.6 linkc.1588G>T p.Val530Phe missense_variant Exon 12 of 12 5 NM_031464.5 ENSP00000450567.1 Q9Y6S9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1588G>T (p.V530F) alteration is located in exon 11 (coding exon 10) of the RPS6KL1 gene. This alteration results from a G to T substitution at nucleotide position 1588, causing the valine (V) at amino acid position 530 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.027
T;T;.;T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.83
T;.;T;.
M_CAP
Benign
0.061
D
MetaRNN
Uncertain
0.45
T;T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.81
L;L;.;L
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-3.9
.;D;D;D
REVEL
Benign
0.24
Sift
Uncertain
0.0020
.;D;T;D
Sift4G
Uncertain
0.0040
D;D;D;D
Polyphen
0.97
D;D;.;D
Vest4
0.27
MutPred
0.62
Loss of ubiquitination at K532 (P = 0.0573);Loss of ubiquitination at K532 (P = 0.0573);.;Loss of ubiquitination at K532 (P = 0.0573);
MVP
0.80
MPC
0.69
ClinPred
0.92
D
GERP RS
0.71
Varity_R
0.45
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-75373779; API