chrX-20155503-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004586.3(RPS6KA3):c.2118A>G(p.Thr706=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 111,851 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)
Consequence
RPS6KA3
NM_004586.3 synonymous
NM_004586.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.777
Genes affected
RPS6KA3 (HGNC:10432): (ribosomal protein S6 kinase A3) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical 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. Mutations in this gene have been associated with Coffin-Lowry syndrome (CLS). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant X-20155503-T-C is Benign according to our data. Variant chrX-20155503-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2930243.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.777 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPS6KA3 | NM_004586.3 | c.2118A>G | p.Thr706= | synonymous_variant | 22/22 | ENST00000379565.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPS6KA3 | ENST00000379565.9 | c.2118A>G | p.Thr706= | synonymous_variant | 22/22 | 1 | NM_004586.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 111797Hom.: 0 Cov.: 22 AF XY: 0.0000294 AC XY: 1AN XY: 33983
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GnomAD4 exome Cov.: 29
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29
GnomAD4 genome ? AF: 0.0000179 AC: 2AN: 111851Hom.: 0 Cov.: 22 AF XY: 0.0000294 AC XY: 1AN XY: 34047
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Coffin-Lowry syndrome;C0796225:Intellectual disability, X-linked 19 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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