rs10484520

chr6-166801198-G-A

Variant summary

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

The XR_007059865.1(LOC124901459):n.184C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 152,164 control chromosomes in the GnomAD database, including 545 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 0.043 (545 hom., cov: 33)
• Consequence: LOC124901459 XR_007059865.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

Genes affected

LOC124901459 (HGNC:):

RPS6KA2 (HGNC:10431): (ribosomal protein S6 kinase A2) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains two non-identical 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. Alternative splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124901459	XR_007059865.1	n.184C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.123+57002C>T		intron_variant		2
RPS6KA2	ENST00000506565.1	c.124-30285C>T		intron_variant		4
RPS6KA2	ENST00000510118.5	c.124-30285C>T		intron_variant		2
RPS6KA2	ENST00000512860.5	c.-169+105160C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6480 AN: 152046 Hom.: 544 Cov.: 33

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0353

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0426 AC: 6486 AN: 152164 Hom.: 545 Cov.: 33 AF XY: 0.0483 AC XY: 3594 AN XY: 74412

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.0693

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0785

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.0373

Alfa AF: 0.0364 Hom.: 44

Bravo AF: 0.0429

Asia WGS AF: 0.267 AC: 926 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.0
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10484520; hg19: chr6-167214686;