chr14-90894459-C-T

Variant names:

• chr14-90894459-C-T
• NM_004755.4:c.1598G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004755.4(RPS6KA5):​c.1598G>A​(p.Ser533Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS6KA5 NM_004755.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA5	NM_004755.4	MANE Select	c.1598G>A	p.Ser533Asn	missense	Exon 13 of 17	NP_004746.2
	RPS6KA5	NM_001322229.2		c.1598G>A	p.Ser533Asn	missense	Exon 13 of 17	NP_001309158.1
	RPS6KA5	NM_001322236.2		c.1514G>A	p.Ser505Asn	missense	Exon 12 of 16	NP_001309165.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA5	ENST00000614987.5	TSL:1 MANE Select	c.1598G>A	p.Ser533Asn	missense	Exon 13 of 17	ENSP00000479667.1	O75582-1
	RPS6KA5	ENST00000418736.6	TSL:1	c.1598G>A	p.Ser533Asn	missense	Exon 13 of 13	ENSP00000402787.2	O75582-2
	RPS6KA5	ENST00000886639.1		c.1631G>A	p.Ser544Asn	missense	Exon 13 of 17	ENSP00000556698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.059
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.53	N
PhyloP100		6.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.087
Sift	Benign	0.096	T
Sift4G	Benign	0.28	T
Polyphen		0.080	B
Vest4		0.61
MutPred		0.48		Gain of catalytic residue at D537 (P = 0)
MVP		0.58
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.55
gMVP		0.75
Mutation Taster		=41/59	disease causing

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

Other links and lift over

hg19: chr14-91360803;