chr14-74907493-T-C

Variant names:

• chr14-74907493-T-C
• NM_031464.5:c.1481A>G

Variant summary

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

The NM_031464.5(RPS6KL1):​c.1481A>G​(p.His494Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.26
• 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.1481A>G	p.His494Arg	missense	Exon 11 of 12	NP_113652.2	Q9Y6S9-1
	RPS6KL1	NM_001370252.1		c.1481A>G	p.His494Arg	missense	Exon 10 of 11	NP_001357181.1
	RPS6KL1	NM_001370253.1		c.1436A>G	p.His479Arg	missense	Exon 11 of 11	NP_001357182.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KL1	ENST00000557413.6	TSL:5 MANE Select	c.1481A>G	p.His494Arg	missense	Exon 11 of 12	ENSP00000450567.1	Q9Y6S9-1
	RPS6KL1	ENST00000555009.5	TSL:1	n.1388A>G		non_coding_transcript_exon	Exon 9 of 12	ENSP00000450660.1	Q9Y6S9-2
	RPS6KL1	ENST00000961459.1		c.1529A>G	p.His510Arg	missense	Exon 12 of 13	ENSP00000631518.1

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	Uncertain	0.45
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.73
MutPred		0.40		Loss of glycosylation at S489 (P = 0.1099)
MVP		0.37
MPC		0.72
ClinPred		0.99	D
GERP RS		5.7
PromoterAI		-0.13	Neutral
Varity_R		0.65
gMVP		0.65
Mutation Taster		=10/90	disease causing

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: chr14-75374196;