14-90900165-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_004755.4(RPS6KA5):c.1322G>A(p.Arg441Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000038 in 1,606,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
RPS6KA5
NM_004755.4 missense
NM_004755.4 missense
Scores
4
6
6
Clinical Significance
Conservation
PhyloP100: 7.87
Genes affected
RPS6KA5 (HGNC:10434): (ribosomal protein S6 kinase A5) Enables ATP binding activity and protein serine/threonine kinase activity. Involved in several processes, including histone-serine phosphorylation; positive regulation of histone modification; and regulation of transcription, DNA-templated. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.749
BS2
?
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPS6KA5 | NM_004755.4 | c.1322G>A | p.Arg441Gln | missense_variant | 11/17 | ENST00000614987.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPS6KA5 | ENST00000614987.5 | c.1322G>A | p.Arg441Gln | missense_variant | 11/17 | 1 | NM_004755.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152068Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000522 AC: 13AN: 249022Hom.: 0 AF XY: 0.0000668 AC XY: 9AN XY: 134738
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GnomAD4 exome AF: 0.0000378 AC: 55AN: 1453866Hom.: 0 Cov.: 30 AF XY: 0.0000277 AC XY: 20AN XY: 723202
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74374
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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 submitter | clinical testing | Ambry Genetics | Feb 14, 2023 | The c.1322G>A (p.R441Q) alteration is located in exon 11 (coding exon 11) of the RPS6KA5 gene. This alteration results from a G to A substitution at nucleotide position 1322, causing the arginine (R) at amino acid position 441 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
T;T;T
Polyphen
D;.;D
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 19
Find out detailed SpliceAI scores and Pangolin per-transcript scores at