rs3213717

chr14-74911644-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031464.5(RPS6KL1):c.531+150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 749,144 control chromosomes in the GnomAD database, including 9,661 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1501 hom., cov: 32)
  • Exomes 𝑓: 0.15 (8160 hom.)
• Consequence: RPS6KL1 NM_031464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KL1	NM_031464.5	c.531+150G>A		intron_variant		ENST00000557413.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KL1	ENST00000557413.6	c.531+150G>A		intron_variant		5	NM_031464.5	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19922 AN: 151922 Hom.: 1503 Cov.: 32

Gnomad AFR AF: 0.0830

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.153 AC: 91558 AN: 597102 Hom.: 8160 Cov.: 8 AF XY: 0.159 AC XY: 49786 AN XY: 312954

Gnomad4 AFR exome AF: 0.0793

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.0902

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.131 AC: 19919 AN: 152042 Hom.: 1501 Cov.: 32 AF XY: 0.137 AC XY: 10212 AN XY: 74284

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.115

Alfa AF: 0.125 Hom.: 150

Bravo AF: 0.120

Asia WGS AF: 0.208 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.1
Dann	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs3213717; hg19: chr14-75378347; COSMIC: COSV63580820; COSMIC: COSV63580820;