Genetic Variant RPS6KA5:p.Gly9Cys (chr14-91060410-C-A) – 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_001322235.2(RPS6KA5):c.-353G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,355,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

RPS6KA5
NM_001322235.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.620

Publications

0 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:

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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=0.23488805).

BS2

High AC in GnomAdExome4 at 46 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322235.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS6KA5	NM_004755.4	MANE Select	c.25G>T	p.Gly9Cys	missense	Exon 1 of 17	NP_004746.2
RPS6KA5	NM_001322235.2		c.-353G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_001309164.1	O75582-3
RPS6KA5	NM_001322234.2		c.-589G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 17	NP_001309163.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS6KA5	ENST00000614987.5	TSL:1 MANE Select	c.25G>T	p.Gly9Cys	missense	Exon 1 of 17	ENSP00000479667.1	O75582-1
RPS6KA5	ENST00000418736.6	TSL:1	c.25G>T	p.Gly9Cys	missense	Exon 1 of 13	ENSP00000402787.2	O75582-2
RPS6KA5	ENST00000554206.1	TSL:1	n.25G>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000450591.1	G3V2D1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000111

AC:

AN:

180508

AF XY:

0.00000987

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:

0.0000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000339

AC:

AN:

1355838

Hom.:

Cov.:

AF XY:

0.0000327

AC XY:

AN XY:

672772

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28466

American (AMR)

AF:

0.00

AC:

AN:

35080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23384

East Asian (EAS)

AF:

0.00

AC:

AN:

32200

South Asian (SAS)

AF:

0.00

AC:

AN:

73582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5352

European-Non Finnish (NFE)

AF:

0.0000427

AC:

AN:

1053994

Other (OTH)

AF:

0.0000183

AC:

AN:

54734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000167

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

0.12

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.0

PhyloP100

0.62

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.23

REVEL

Benign

0.17

Sift

Benign

0.050

Sift4G

Uncertain

0.057

Polyphen

0.94

Vest4

0.34

MVP

0.56

ClinPred

0.26

GERP RS

3.2

PromoterAI

-0.077

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.73

Mutation Taster

=91/9

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