dbSNP rs765224867: RPS6KA5:p.Gly18Arg (chr14-91060383-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004755.4(RPS6KA5):c.52G>C(p.Gly18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,508,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

RPS6KA5
NM_004755.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.227

Publications

1 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:

DGLUCY (HGNC:20498): (D-glutamate cyclase) Predicted to enable D-glutamate cyclase activity. Predicted to be involved in glutamate metabolic process. Predicted to be located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

DGLUCY links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11789781).

BS2

High AC in GnomAd4 at 6 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.52G>C	p.Gly18Arg	missense	Exon 1 of 17	NP_004746.2
RPS6KA5	NM_001322229.2		c.52G>C	p.Gly18Arg	missense	Exon 1 of 17	NP_001309158.1
RPS6KA5	NM_001322236.2		c.52G>C	p.Gly18Arg	missense	Exon 1 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.52G>C	p.Gly18Arg	missense	Exon 1 of 17	ENSP00000479667.1	O75582-1
RPS6KA5	ENST00000418736.6	TSL:1	c.52G>C	p.Gly18Arg	missense	Exon 1 of 13	ENSP00000402787.2	O75582-2
RPS6KA5	ENST00000554206.1	TSL:1	n.52G>C		non_coding_transcript_exon	Exon 1 of 10	ENSP00000450591.1	G3V2D1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000673

AC:

AN:

178186

AF XY:

0.0000796

show subpopulations

Gnomad AFR exome

AF:

0.000116

Gnomad AMR exome

AF:

0.000161

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000873

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000700

AC:

AN:

1356850

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

673186

show subpopulations

African (AFR)

AF:

0.0000352

AC:

AN:

28442

American (AMR)

AF:

0.0000855

AC:

AN:

35070

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23504

East Asian (EAS)

AF:

0.00

AC:

AN:

32110

South Asian (SAS)

AF:

0.00

AC:

AN:

73976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5364

European-Non Finnish (NFE)

AF:

0.0000806

AC:

AN:

1055122

Other (OTH)

AF:

0.000109

AC:

AN:

54842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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

AF:

0.0000395

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000753

AC:

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

0.15

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.23

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.44

REVEL

Benign

0.051

Sift

Uncertain

0.024

Sift4G

Benign

0.14

Polyphen

0.50

Vest4

0.17

MutPred

0.30

Gain of catalytic residue at G19 (P = 0.0094)

MVP

0.50

ClinPred

0.082

GERP RS

1.8

PromoterAI

-0.053

Neutral

(source)

Varity_R

0.042

gMVP

0.56

Mutation Taster

=83/17

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over