rs1465450200

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031464.5(RPS6KL1):​c.1072G>T​(p.Gly358Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RPS6KL1 NM_031464.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26685202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KL1	NM_031464.5	c.1072G>T	p.Gly358Cys	missense_variant	Exon 8 of 12	ENST00000557413.6	NP_113652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KL1	ENST00000557413.6	c.1072G>T	p.Gly358Cys	missense_variant	Exon 8 of 12	5	NM_031464.5	ENSP00000450567.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000417 AC: 1 AN: 239994 Hom.: 0 AF XY: 0.00000760 AC XY: 1 AN XY: 131544

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455450 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724262

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0070	T;T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.71	T;.;.
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	M;M;M
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	.;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0050	.;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.96	D;D;D
Vest4		0.37
MutPred		0.56		Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);
MVP		0.67
MPC		0.56
ClinPred		0.78	D
GERP RS		3.3
Varity_R		0.22
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1465450200; hg19: chr14-75376444;