NM_002953.4:c.31C>G

Variant names:

• chr1-26529951-C-G
• rs560501416
• NM_002953.4:c.31C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002953.4(RPS6KA1):​c.31C>G​(p.Pro11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,433,776 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0022 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (30 hom.)
• Consequence: RPS6KA1 NM_002953.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429
• Publications: 1 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]

LOC124903884 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049789846).
• BS2: High AC in GnomAd4 at 337 AD gene.

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.31C>G	p.Pro11Ala	missense	Exon 1 of 22	NP_002944.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA1	ENST00000374168.7	TSL:1 MANE Select	c.31C>G	p.Pro11Ala	missense	Exon 1 of 22	ENSP00000363283.2	Q15418-1
	RPS6KA1	ENST00000952528.1		c.31C>G	p.Pro11Ala	missense	Exon 1 of 22	ENSP00000622587.1
	RPS6KA1	ENST00000952527.1		c.31C>G	p.Pro11Ala	missense	Exon 1 of 22	ENSP00000622586.1

Frequencies

GnomAD3 genomes AF: 0.00222 AC: 337 AN: 151540 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.000532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00191

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0000964

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.00385

GnomAD2 exomes AF: 0.00417 AC: 302 AN: 72384 AF XY: 0.00405

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.0259

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.00259 AC: 3316 AN: 1282130 Hom.: 30 Cov.: 29 AF XY: 0.00259 AC XY: 1639 AN XY: 632638

African (AFR) AF: 0.000351 AC: 9 AN: 25672

American (AMR) AF: 0.00212 AC: 50 AN: 23596

Ashkenazi Jewish (ASJ) AF: 0.0264 AC: 577 AN: 21820

East Asian (EAS) AF: 0.0000386 AC: 1 AN: 25920

South Asian (SAS) AF: 0.00334 AC: 237 AN: 70866

European-Finnish (FIN) AF: 0.0000630 AC: 2 AN: 31744

Middle Eastern (MID) AF: 0.00626 AC: 23 AN: 3674

European-Non Finnish (NFE) AF: 0.00213 AC: 2186 AN: 1026874

Other (OTH) AF: 0.00445 AC: 231 AN: 51964

GnomAD4 genome AF: 0.00222 AC: 337 AN: 151646 Hom.: 4 Cov.: 31 AF XY: 0.00220 AC XY: 163 AN XY: 74104

African (AFR) AF: 0.000530 AC: 22 AN: 41476

American (AMR) AF: 0.00190 AC: 29 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4824

European-Finnish (FIN) AF: 0.0000964 AC: 1 AN: 10374

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00245 AC: 166 AN: 67812

Other (OTH) AF: 0.00381 AC: 8 AN: 2100

Alfa AF: 0.000850 Hom.: 0

Bravo AF: 0.00221

ExAC AF: 0.00437 AC: 82

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.066
FATHMM_MKL	Benign	0.33	N
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.43
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.15
Sift	Benign	0.79	T
Sift4G	Benign	0.74	T
Polyphen		0.81	P
Vest4		0.24
MVP		0.74
ClinPred		0.080	T
GERP RS		3.0
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.068
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs560501416; hg19: chr1-26856442;