14-90872111-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004755.4(RPS6KA5):c.2372C>T(p.Pro791Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000057 ( 0 hom. )
Consequence
RPS6KA5
NM_004755.4 missense
NM_004755.4 missense
Scores
1
5
10
Clinical Significance
Conservation
PhyloP100: 7.33
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 -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1650353).
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.2372C>T | p.Pro791Leu | missense_variant | 17/17 | ENST00000614987.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPS6KA5 | ENST00000614987.5 | c.2372C>T | p.Pro791Leu | missense_variant | 17/17 | 1 | NM_004755.4 | P1 | |
RPS6KA5 | ENST00000536315.6 | c.2135C>T | p.Pro712Leu | missense_variant | 17/17 | 2 | |||
RPS6KA5 | ENST00000556178.5 | c.*1842C>T | 3_prime_UTR_variant, NMD_transcript_variant | 14/14 | 5 | ||||
RPS6KA5 | ENST00000648062.1 | c.*1998C>T | 3_prime_UTR_variant, NMD_transcript_variant | 19/19 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151910Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000956 AC: 24AN: 250950Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135592
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GnomAD4 exome AF: 0.0000575 AC: 84AN: 1461724Hom.: 0 Cov.: 31 AF XY: 0.0000963 AC XY: 70AN XY: 727156
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151910Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 5AN XY: 74178
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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 | Oct 26, 2022 | The c.2372C>T (p.P791L) alteration is located in exon 17 (coding exon 17) of the RPS6KA5 gene. This alteration results from a C to T substitution at nucleotide position 2372, causing the proline (P) at amino acid position 791 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at