1-26546063-A-G

Variant names:

• chr1-26546063-A-G
• rs12723936
• NM_002953.4:c.109-804A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006665.2(RPS6KA1):​c.135+28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,606,354 control chromosomes in the GnomAD database, including 84,393 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 0.36 (10852 hom., cov: 33)
  • Exomes 𝑓: 0.30 (73541 hom.)
• Consequence: RPS6KA1 NM_001006665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006665.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA1	NM_002953.4	MANE Select	c.109-804A>G		intron	N/A	NP_002944.2
	RPS6KA1	NM_001006665.2		c.135+28A>G		intron	N/A	NP_001006666.1
	RPS6KA1	NM_001330441.2		c.61-804A>G		intron	N/A	NP_001317370.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA1	ENST00000374168.7	TSL:1 MANE Select	c.109-804A>G		intron	N/A	ENSP00000363283.2
	RPS6KA1	ENST00000531382.5	TSL:2	c.135+28A>G		intron	N/A	ENSP00000435412.1
	RPS6KA1	ENST00000952528.1		c.109-804A>G		intron	N/A	ENSP00000622587.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54379 AN: 151950 Hom.: 10849 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.372 AC: 86406 AN: 232264 AF XY: 0.368

Gnomad AFR exome AF: 0.474

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.771

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.300 AC: 435670 AN: 1454284 Hom.: 73541 Cov.: 33 AF XY: 0.303 AC XY: 219223 AN XY: 723592

African (AFR) AF: 0.471 AC: 15504 AN: 32896

American (AMR) AF: 0.407 AC: 17816 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 7242 AN: 25906

East Asian (EAS) AF: 0.752 AC: 29117 AN: 38720

South Asian (SAS) AF: 0.478 AC: 40907 AN: 85596

European-Finnish (FIN) AF: 0.293 AC: 15337 AN: 52424

Middle Eastern (MID) AF: 0.303 AC: 1716 AN: 5670

European-Non Finnish (NFE) AF: 0.260 AC: 288196 AN: 1109216

Other (OTH) AF: 0.330 AC: 19835 AN: 60086

GnomAD4 genome AF: 0.358 AC: 54413 AN: 152070 Hom.: 10852 Cov.: 33 AF XY: 0.363 AC XY: 26982 AN XY: 74338

African (AFR) AF: 0.475 AC: 19703 AN: 41482

American (AMR) AF: 0.365 AC: 5586 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3470

East Asian (EAS) AF: 0.765 AC: 3936 AN: 5148

South Asian (SAS) AF: 0.509 AC: 2455 AN: 4826

European-Finnish (FIN) AF: 0.282 AC: 2991 AN: 10588

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.259 AC: 17594 AN: 67950

Other (OTH) AF: 0.359 AC: 759 AN: 2112

Alfa AF: 0.282 Hom.: 1205

Bravo AF: 0.369

Asia WGS AF: 0.608 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		-0.13
PromoterAI		0.044	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12723936; hg19: chr1-26872554; COSMIC: COSV64809558; COSMIC: COSV64809558;