14-74907076-C-A

Variant names:

• chr14-74907076-C-A
• NM_031464.5:c.1588G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031464.5(RPS6KL1):​c.1588G>T​(p.Val530Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS6KL1 NM_031464.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• Publications: 0 publications found

Genes affected

RPS6KL1 (HGNC:20222): (ribosomal protein S6 kinase like 1) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be located in ribosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031464.5. 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
	RPS6KL1	NM_031464.5	MANE Select	c.1588G>T	p.Val530Phe	missense	Exon 12 of 12	NP_113652.2	Q9Y6S9-1
	RPS6KL1	NM_001370255.1		c.886G>T	p.Val296Phe	missense	Exon 10 of 11	NP_001357184.1
	RPS6KL1	NM_001370256.1		c.892G>T	p.Val298Phe	missense	Exon 9 of 9	NP_001357185.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KL1	ENST00000557413.6	TSL:5 MANE Select	c.1588G>T	p.Val530Phe	missense	Exon 12 of 12	ENSP00000450567.1	Q9Y6S9-1
	RPS6KL1	ENST00000555910.5	TSL:1	c.70G>T	p.Val24Phe	missense	Exon 2 of 3	ENSP00000451986.1	H0YJR0
	RPS6KL1	ENST00000555009.5	TSL:1	n.1495G>T		non_coding_transcript_exon	Exon 10 of 12	ENSP00000450660.1	Q9Y6S9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.15
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.0
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.97	D
Vest4		0.27
MutPred		0.62		Loss of ubiquitination at K532 (P = 0.0573)
MVP		0.80
MPC		0.69
ClinPred		0.92	D
GERP RS		0.71
PromoterAI		-0.044	Neutral
Varity_R		0.45
gMVP		0.77
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr14-75373779;