X-84106963-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014496.5(RPS6KA6):​c.1189G>A​(p.Glu397Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,081,786 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000028 ( 0 hom. 0 hem. )

Consequence

RPS6KA6
NM_014496.5 missense

Scores

2
3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47
Variant links:
Genes affected
RPS6KA6 (HGNC:10435): (ribosomal protein S6 kinase A6) This gene encodes a member of ribosomal S6 kinase family, serine-threonine protein kinases which are regulated by growth factors. The encoded protein may be distinct from other members of this family, however, as studies suggest it is not growth factor dependent and may not participate in the same signaling pathways. [provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38654763).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS6KA6NM_014496.5 linkuse as main transcriptc.1189G>A p.Glu397Lys missense_variant 14/22 ENST00000262752.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS6KA6ENST00000262752.5 linkuse as main transcriptc.1189G>A p.Glu397Lys missense_variant 14/221 NM_014496.5 P1Q9UK32-1
RPS6KA6ENST00000620340.4 linkuse as main transcriptc.1189G>A p.Glu397Lys missense_variant 14/225 Q9UK32-2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000277
AC:
3
AN:
1081786
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
349200
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:
0.00000362
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

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 GeneticsNov 08, 2021The c.1189G>A (p.E397K) alteration is located in exon 14 (coding exon 14) of the RPS6KA6 gene. This alteration results from a G to A substitution at nucleotide position 1189, causing the glutamic acid (E) at amino acid position 397 to be replaced by a lysine (K). 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
0.13
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
.;T
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.78
T;T
M_CAP
Pathogenic
0.31
D
MetaRNN
Benign
0.39
T;T
MetaSVM
Benign
-0.73
T
MutationAssessor
Uncertain
2.7
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-1.9
.;N
REVEL
Benign
0.24
Sift
Benign
0.32
.;T
Sift4G
Benign
0.51
T;T
Polyphen
0.13
.;B
Vest4
0.13
MutPred
0.50
Gain of ubiquitination at E397 (P = 0.0238);Gain of ubiquitination at E397 (P = 0.0238);
MVP
0.75
MPC
0.59
ClinPred
0.90
D
GERP RS
4.9
Varity_R
0.57
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chrX-83361971; API