Variant 14-91060343-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004755.4(RPS6KA5):c.92A>T(p.Glu31Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000079 in 1,265,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

RPS6KA5
NM_004755.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA5	NM_004755.4 linkuse as main transcript	c.92A>T	p.Glu31Val	missense_variant	1/17	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.92A>T	p.Glu31Val	missense_variant	1/17	1	NM_004755.4	ENSP00000479667	P1	O75582-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.90e-7

AC:

AN:

1265820

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

621494

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:

9.93e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 23, 2021

The c.92A>T (p.E31V) alteration is located in exon 1 (coding exon 1) of the RPS6KA5 gene. This alteration results from a A to T substitution at nucleotide position 92, causing the glutamic acid (E) at amino acid position 31 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.32

T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.86

D;D

M_CAP

Pathogenic

0.90

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.99

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-2.1

.;N

REVEL

Benign

0.28

Sift

Benign

0.071

.;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0020

B;B

Vest4

0.53

MutPred

0.47

Loss of disorder (P = 0.0278);Loss of disorder (P = 0.0278);

MVP

0.60

ClinPred

0.31

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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