chr14-74907076-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KL1	NM_031464.5	c.1588G>T	p.Val530Phe	missense_variant	Exon 12 of 12	ENST00000557413.6	NP_113652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KL1	ENST00000557413.6	c.1588G>T	p.Val530Phe	missense_variant	Exon 12 of 12	5	NM_031464.5	ENSP00000450567.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1588G>T (p.V530F) alteration is located in exon 11 (coding exon 10) of the RPS6KL1 gene. This alteration results from a G to T substitution at nucleotide position 1588, causing the valine (V) at amino acid position 530 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.83	T;.;T;.
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.81	L;L;.;L
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.9	.;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	.;D;T;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.97	D;D;.;D
Vest4		0.27
MutPred		0.62		Loss of ubiquitination at K532 (P = 0.0573);Loss of ubiquitination at K532 (P = 0.0573);.;Loss of ubiquitination at K532 (P = 0.0573);
MVP		0.80
MPC		0.69
ClinPred		0.92	D
GERP RS		0.71
Varity_R		0.45
gMVP		0.77

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-75373779;