1-26551710-GG-AA

Variant names:

• chr1-26551710-GG-AA
• NM_002953.4:c.455_456delGGinsAA
• RPS6KA1 p.Arg152Gln

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_002953.4(RPS6KA1):​c.455_456delGGinsAA​(p.Arg152Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R152W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPS6KA1 NM_002953.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.14
• Publications: 0 publications found

Genes affected

RPS6KA1 (HGNC:10430): (ribosomal protein S6 kinase A1) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical 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. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002953.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA1	NM_002953.4	MANE Select	c.455_456delGGinsAA	p.Arg152Gln	missense	N/A	NP_002944.2
	RPS6KA1	NM_001006665.2		c.482_483delGGinsAA	p.Arg161Gln	missense	N/A	NP_001006666.1	Q15418-2
	RPS6KA1	NM_001330441.2		c.407_408delGGinsAA	p.Arg136Gln	missense	N/A	NP_001317370.1	Q15418-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA1	ENST00000374168.7	TSL:1 MANE Select	c.455_456delGGinsAA	p.Arg152Gln	missense	N/A	ENSP00000363283.2	Q15418-1
	RPS6KA1	ENST00000531382.5	TSL:2	c.482_483delGGinsAA	p.Arg161Gln	missense	N/A	ENSP00000435412.1	Q15418-2
	RPS6KA1	ENST00000952528.1		c.455_456delGGinsAA	p.Arg152Gln	missense	N/A	ENSP00000622587.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-26878201;