rs1465450200

Variant names:

• chr14-74909741-C-G
• rs1465450200
• NM_031464.5:c.1072G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-74909741-C-G
• chr14-74909741-C-A
• chr14-74909741-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031464.5(RPS6KL1):​c.1072G>C​(p.Gly358Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: RPS6KL1 NM_031464.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.406
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22513592).

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.1072G>C	p.Gly358Arg	missense	Exon 8 of 12	NP_113652.2	Q9Y6S9-1
	RPS6KL1	NM_001370252.1		c.1072G>C	p.Gly358Arg	missense	Exon 7 of 11	NP_001357181.1
	RPS6KL1	NM_001370253.1		c.1027G>C	p.Gly343Arg	missense	Exon 8 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.1072G>C	p.Gly358Arg	missense	Exon 8 of 12	ENSP00000450567.1	Q9Y6S9-1
	RPS6KL1	ENST00000555009.5	TSL:1	n.979G>C		non_coding_transcript_exon	Exon 6 of 12	ENSP00000450660.1	Q9Y6S9-2
	RPS6KL1	ENST00000961459.1		c.1120G>C	p.Gly374Arg	missense	Exon 9 of 13	ENSP00000631518.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74366

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.000196 AC: 3 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000343967), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.41
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.16
Sift	Benign	0.11	T
Sift4G	Uncertain	0.058	T
Polyphen		0.64	P
Vest4		0.41
MutPred		0.64		Gain of methylation at G358 (P = 0.0314)
MVP		0.63
MPC		0.21
ClinPred		0.31	T
GERP RS		3.3
Varity_R		0.065
gMVP		0.56
Mutation Taster		=97/3	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

dbSNP: rs1465450200; hg19: chr14-75376444;