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GeneBe

11-64361871-C-T

Variant summary

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

The NM_003942.3(RPS6KA4):c.775C>T(p.Pro259Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,544 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RPS6KA4
NM_003942.3 missense

Scores

3
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49
Variant links:
Genes affected
RPS6KA4 (HGNC:10433): (ribosomal protein S6 kinase A4) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including CREB1 and ATF1. The encoded protein can also phosphorylate histone H3 to regulate certain inflammatory genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS6KA4NM_003942.3 linkuse as main transcriptc.775C>T p.Pro259Ser missense_variant 8/17 ENST00000334205.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS6KA4ENST00000334205.9 linkuse as main transcriptc.775C>T p.Pro259Ser missense_variant 8/171 NM_003942.3 P1O75676-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1460544
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726626
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 02, 2021The c.775C>T (p.P259S) alteration is located in exon 8 (coding exon 8) of the RPS6KA4 gene. This alteration results from a C to T substitution at nucleotide position 775, causing the proline (P) at amino acid position 259 to be replaced by a serine (S). 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
Pathogenic
0.93
BayesDel_addAF
Benign
-0.066
T
BayesDel_noAF
Benign
-0.33
Cadd
Pathogenic
29
Dann
Pathogenic
1.0
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.43
T;T;T
MetaSVM
Benign
-0.38
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-6.3
D;D;D
REVEL
Benign
0.26
Sift
Benign
0.041
D;T;T
Sift4G
Benign
0.15
T;T;T
Polyphen
0.13
B;D;.
Vest4
0.39
MutPred
0.33
Loss of glycosylation at P259 (P = 0.039);Loss of glycosylation at P259 (P = 0.039);.;
MVP
0.54
MPC
1.2
ClinPred
0.96
D
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.43
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr11-64129343; API