NM_014496.5:c.1189G>A

Variant names:

• chrX-84106963-C-T
• NM_014496.5:c.1189G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014496.5(RPS6KA6):​c.1189G>A​(p.Glu397Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,081,786 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000028 (0 hom. 0 hem.)
• Consequence: RPS6KA6 NM_014496.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.47
• Publications: 0 publications found

Genes affected

RPS6KA6 (HGNC:10435): (ribosomal protein S6 kinase A6) This gene encodes a member of ribosomal S6 kinase family, serine-threonine protein kinases which are regulated by growth factors. The encoded protein may be distinct from other members of this family, however, as studies suggest it is not growth factor dependent and may not participate in the same signaling pathways. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38654763).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014496.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA6	NM_014496.5	MANE Select	c.1189G>A	p.Glu397Lys	missense	Exon 14 of 22	NP_055311.1	Q9UK32-1
	RPS6KA6	NM_001330512.1		c.1189G>A	p.Glu397Lys	missense	Exon 16 of 24	NP_001317441.1	Q9UK32-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA6	ENST00000262752.5	TSL:1 MANE Select	c.1189G>A	p.Glu397Lys	missense	Exon 14 of 22	ENSP00000262752.2	Q9UK32-1
	RPS6KA6	ENST00000620340.4	TSL:5	c.1189G>A	p.Glu397Lys	missense	Exon 14 of 22	ENSP00000483896.1	Q9UK32-2
	RPS6KA6	ENST00000911420.1		c.1189G>A	p.Glu397Lys	missense	Exon 14 of 22	ENSP00000581479.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000277 AC: 3 AN: 1081786 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 349200

African (AFR) AF: 0.00 AC: 0 AN: 26078

American (AMR) AF: 0.00 AC: 0 AN: 34607

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19201

East Asian (EAS) AF: 0.00 AC: 0 AN: 29954

South Asian (SAS) AF: 0.00 AC: 0 AN: 52749

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4094

European-Non Finnish (NFE) AF: 0.00000362 AC: 3 AN: 829179

Other (OTH) AF: 0.00 AC: 0 AN: 45502

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.24
Sift	Benign	0.32	T
Sift4G	Benign	0.51	T
Polyphen		0.13	B
Vest4		0.13
MutPred		0.50		Gain of ubiquitination at E397 (P = 0.0238)
MVP		0.75
MPC		0.59
ClinPred		0.90	D
GERP RS		4.9
Varity_R		0.57
gMVP		0.38
Mutation Taster		=62/38	polymorphism

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

hg19: chrX-83361971;