Variant 14-90875306-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004755.4(RPS6KA5):c.1891T>C(p.Cys631Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RPS6KA5
NM_004755.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06

Variant links:

Genes affected

RPS6KA5 (HGNC:10434): (ribosomal protein S6 kinase A5) Enables ATP binding activity and protein serine/threonine kinase activity. Involved in several processes, including histone-serine phosphorylation; positive regulation of histone modification; and regulation of transcription, DNA-templated. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RPS6KA5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA5	NM_004755.4 linkuse as main transcript	c.1891T>C	p.Cys631Arg	missense_variant	15/17	ENST00000614987.5	NP_004746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA5	ENST00000614987.5 linkuse as main transcript	c.1891T>C	p.Cys631Arg	missense_variant	15/17	1	NM_004755.4	ENSP00000479667	P1	O75582-1
RPS6KA5	ENST00000536315.6 linkuse as main transcript	c.1654T>C	p.Cys552Arg	missense_variant	15/17	2		ENSP00000442803		O75582-3
RPS6KA5	ENST00000556178.5 linkuse as main transcript	c.*1361T>C		3_prime_UTR_variant, NMD_transcript_variant	12/14	5		ENSP00000451305
RPS6KA5	ENST00000648062.1 linkuse as main transcript	c.*1517T>C		3_prime_UTR_variant, NMD_transcript_variant	17/19			ENSP00000497354

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251120

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.1891T>C (p.C631R) alteration is located in exon 15 (coding exon 15) of the RPS6KA5 gene. This alteration results from a T to C substitution at nucleotide position 1891, causing the cysteine (C) at amino acid position 631 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.0050

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.064

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.0095

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.090

.;N

REVEL

Benign

0.16

Sift

Benign

0.54

.;T

Sift4G

Benign

0.55

T;T

Polyphen

0.019

B;.

Vest4

0.64

MutPred

0.57

Gain of disorder (P = 0.0039);.;

MVP

0.54

ClinPred

0.28

GERP RS

5.4

Varity_R

0.67

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over