Genetic Variant NM_004755.4:c.1891T>C (chr14-90875306-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 13/22 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

Publications

3 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004755.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RPS6KA5	NM_004755.4	MANE Select	c.1891T>C	p.Cys631Arg	missense	Exon 15 of 17	NP_004746.2
RPS6KA5	NM_001322229.2		c.1870T>C	p.Cys624Arg	missense	Exon 15 of 17	NP_001309158.1
RPS6KA5	NM_001322236.2		c.1807T>C	p.Cys603Arg	missense	Exon 14 of 16	NP_001309165.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS6KA5	ENST00000614987.5	TSL:1 MANE Select	c.1891T>C	p.Cys631Arg	missense	Exon 15 of 17	ENSP00000479667.1	O75582-1
RPS6KA5	ENST00000886639.1		c.1924T>C	p.Cys642Arg	missense	Exon 15 of 17	ENSP00000556698.1
RPS6KA5	ENST00000886636.1		c.1870T>C	p.Cys624Arg	missense	Exon 15 of 17	ENSP00000556695.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251120

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111870

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.0050

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.064

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.0095

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

PhyloP100

5.1

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.090

REVEL

Benign

0.16

Sift

Benign

0.54

Sift4G

Benign

0.55

Polyphen

0.019

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

Mutation Taster

=52/48

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over