NM_002953.4:c.724A>G

Variant summary

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

The NM_002953.4(RPS6KA1):​c.724A>G​(p.Ser242Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S242C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RPS6KA1
NM_002953.4 missense

Scores

1
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.31
Variant links:
Genes affected
RPS6KA1 (HGNC:10430): (ribosomal protein S6 kinase A1) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
MIR1976 (HGNC:37064): (microRNA 1976) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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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
RPS6KA1NM_002953.4 linkc.724A>G p.Ser242Gly missense_variant Exon 9 of 22 ENST00000374168.7 NP_002944.2 Q15418-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS6KA1ENST00000374168.7 linkc.724A>G p.Ser242Gly missense_variant Exon 9 of 22 1 NM_002953.4 ENSP00000363283.2 Q15418-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000193
Hom.:
1
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Uncertain
0.048
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;.;.;.;.
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Benign
0.026
D
MetaRNN
Uncertain
0.63
D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;.;.;.;.
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-2.3
N;N;N;N;N
REVEL
Benign
0.23
Sift
Benign
0.035
D;D;D;D;D
Sift4G
Uncertain
0.015
D;D;D;D;D
Polyphen
0.87
P;.;.;.;B
Vest4
0.70
MutPred
0.68
Loss of disorder (P = 0.1256);Loss of disorder (P = 0.1256);.;.;.;
MVP
0.63
MPC
0.75
ClinPred
0.85
D
GERP RS
5.7
Varity_R
0.54
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.32
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.32
Position offset: 0

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: rs1488917029; hg19: chr1-26881197; API