X-84106947-G-A

Position:

• chrX-84106947-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014496.5(RPS6KA6):​c.1205C>T​(p.Thr402Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: RPS6KA6 NM_014496.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20646125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA6	NM_014496.5	c.1205C>T	p.Thr402Ile	missense_variant	14/22	ENST00000262752.5	NP_055311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA6	ENST00000262752.5	c.1205C>T	p.Thr402Ile	missense_variant	14/22	1	NM_014496.5	ENSP00000262752	P1
RPS6KA6	ENST00000620340.4	c.1205C>T	p.Thr402Ile	missense_variant	14/22	5		ENSP00000483896

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.1205C>T (p.T402I) alteration is located in exon 14 (coding exon 14) of the RPS6KA6 gene. This alteration results from a C to T substitution at nucleotide position 1205, causing the threonine (T) at amino acid position 402 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	.;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	T;T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	0.84	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	.;N
REVEL	Benign	0.051
Sift	Benign	0.23	.;T
Sift4G	Benign	0.23	T;T
Polyphen		0.0030	.;B
Vest4		0.18
MutPred		0.41		Gain of methylation at K400 (P = 0.0713);Gain of methylation at K400 (P = 0.0713);
MVP		0.37
MPC		0.55
ClinPred		0.44	T
GERP RS		4.9
Varity_R		0.13
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-83361955;