rs3213716

chr14-74911482-G-Achr14-74911482-G-C

Variant summary

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

The NM_031464.5(RPS6KL1):c.532-102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,356,996 control chromosomes in the GnomAD database, including 101,146 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 0.30 (8714 hom., cov: 31)
  • Exomes 𝑓: 0.39 (92432 hom.)
• Consequence: RPS6KL1 NM_031464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KL1	NM_031464.5	c.532-102C>T		intron_variant		ENST00000557413.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KL1	ENST00000557413.6	c.532-102C>T		intron_variant		5	NM_031464.5	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46288 AN: 151916 Hom.: 8714 Cov.: 31

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.385 AC: 464214 AN: 1204962 Hom.: 92432 Cov.: 16 AF XY: 0.383 AC XY: 229019 AN XY: 598358

Gnomad4 AFR exome AF: 0.0647

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.511

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.304 AC: 46291 AN: 152034 Hom.: 8714 Cov.: 31 AF XY: 0.302 AC XY: 22473 AN XY: 74316

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.341

Alfa AF: 0.353 Hom.: 1572

Bravo AF: 0.311

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.36
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3213716; hg19: chr14-75378185;