chr11-64365341-C-T

Variant names:

• chr11-64365341-C-T
• NM_003942.3:c.947C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003942.3(RPS6KA4):​c.947C>T​(p.Ala316Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS6KA4 NM_003942.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07
• Publications: 0 publications found

Genes affected

RPS6KA4 (HGNC:10433): (ribosomal protein S6 kinase A4) 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 CREB1 and ATF1. The encoded protein can also phosphorylate histone H3 to regulate certain inflammatory genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31219465).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003942.3. 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
	RPS6KA4	NM_003942.3	MANE Select	c.947C>T	p.Ala316Val	missense	Exon 9 of 17	NP_003933.1	O75676-1
	RPS6KA4	NM_001006944.2		c.947C>T	p.Ala316Val	missense	Exon 9 of 17	NP_001006945.1	O75676-2
	RPS6KA4	NM_001300802.2		c.947C>T	p.Ala316Val	missense	Exon 9 of 17	NP_001287731.1	E9PJN1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA4	ENST00000334205.9	TSL:1 MANE Select	c.947C>T	p.Ala316Val	missense	Exon 9 of 17	ENSP00000333896.4	O75676-1
	RPS6KA4	ENST00000528057.5	TSL:1	c.947C>T	p.Ala316Val	missense	Exon 9 of 17	ENSP00000435580.1	E9PJN1
	RPS6KA4	ENST00000969972.1		c.1106C>T	p.Ala369Val	missense	Exon 9 of 17	ENSP00000640031.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.035	D
Polyphen		0.80	P
Vest4		0.51
MutPred		0.58		Gain of methylation at K313 (P = 0.0881)
MVP		0.51
MPC		0.98
ClinPred		0.94	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.40
Mutation Taster		=72/28	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

hg19: chr11-64132813;