14-90920240-C-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004755.4(RPS6KA5):āc.772G>Cā(p.Asp258His) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,611,780 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
RPS6KA5
NM_004755.4 missense
NM_004755.4 missense
Scores
4
6
6
Clinical Significance
Conservation
PhyloP100: 7.03
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 -4 ACMG points.
BS2
?
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPS6KA5 | NM_004755.4 | c.772G>C | p.Asp258His | missense_variant | 7/17 | ENST00000614987.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPS6KA5 | ENST00000614987.5 | c.772G>C | p.Asp258His | missense_variant | 7/17 | 1 | NM_004755.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152074Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249406Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135152
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GnomAD4 exome AF: 0.00000480 AC: 7AN: 1459706Hom.: 0 Cov.: 29 AF XY: 0.00000551 AC XY: 4AN XY: 726244
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74284
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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 | Sep 20, 2023 | The c.772G>C (p.D258H) alteration is located in exon 7 (coding exon 7) of the RPS6KA5 gene. This alteration results from a G to C substitution at nucleotide position 772, causing the aspartic acid (D) at amino acid position 258 to be replaced by a histidine (H). 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
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D;D;T
Polyphen
D;.;D
Vest4
MutPred
Gain of catalytic residue at S253 (P = 0.001);.;Gain of catalytic residue at S253 (P = 0.001);
MVP
ClinPred
D
GERP RS
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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