rs11113

Positions:

• chr1-26574599-C-T

Variant summary

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

The NM_002953.4(RPS6KA1):​c.*398C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 389,256 control chromosomes in the GnomAD database, including 70,859 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 0.61 (28100 hom., cov: 30)
  • Exomes 𝑓: 0.60 (42759 hom.)
• Consequence: RPS6KA1 NM_002953.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

Genes affected

RPS6KA1 (HGNC:10430): (ribosomal protein S6 kinase A1) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA1	NM_002953.4	c.*398C>T		3_prime_UTR_variant	22/22	ENST00000374168.7
RPS6KA1	NM_001006665.2	c.*398C>T		3_prime_UTR_variant	21/21
RPS6KA1	NM_001330441.2	c.*398C>T		3_prime_UTR_variant	21/21
RPS6KA1	XM_024448871.2	c.*398C>T		3_prime_UTR_variant	22/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA1	ENST00000374168.7	c.*398C>T		3_prime_UTR_variant	22/22	1	NM_002953.4	P1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91968 AN: 151706 Hom.: 28086 Cov.: 30

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.596 AC: 141438 AN: 237432 Hom.: 42759 Cov.: 0 AF XY: 0.600 AC XY: 79780 AN XY: 132988

Gnomad4 AFR exome AF: 0.681

Gnomad4 AMR exome AF: 0.612

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.722

Gnomad4 SAS exome AF: 0.646

Gnomad4 FIN exome AF: 0.567

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.592

GnomAD4 genome AF: 0.606 AC: 92030 AN: 151824 Hom.: 28100 Cov.: 30 AF XY: 0.605 AC XY: 44872 AN XY: 74162

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.596

Alfa AF: 0.578 Hom.: 27491

Bravo AF: 0.614

Asia WGS AF: 0.657 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.0
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11113; hg19: chr1-26901090;