NM_004755.4:c.2362A>G

Variant names:

• chr14-90872121-T-C
• rs543409817
• NM_004755.4:c.2362A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004755.4(RPS6KA5):​c.2362A>G​(p.Ser788Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: RPS6KA5 NM_004755.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0210
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.035107195).
• BP6: Variant 14-90872121-T-C is Benign according to our data. Variant chr14-90872121-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3156231.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 26 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA5	NM_004755.4	MANE Select	c.2362A>G	p.Ser788Gly	missense	Exon 17 of 17	NP_004746.2
	RPS6KA5	NM_001322229.2		c.2341A>G	p.Ser781Gly	missense	Exon 17 of 17	NP_001309158.1
	RPS6KA5	NM_001322236.2		c.2278A>G	p.Ser760Gly	missense	Exon 16 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.2362A>G	p.Ser788Gly	missense	Exon 17 of 17	ENSP00000479667.1	O75582-1
	RPS6KA5	ENST00000886639.1		c.2395A>G	p.Ser799Gly	missense	Exon 17 of 17	ENSP00000556698.1
	RPS6KA5	ENST00000886636.1		c.2341A>G	p.Ser781Gly	missense	Exon 17 of 17	ENSP00000556695.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151826 Hom.: 0 Cov.: 31

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: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000637 AC: 16 AN: 251054 AF XY: 0.0000663

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: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461794 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111960

Other (OTH) AF: 0.0000497 AC: 3 AN: 60392

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151944 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74272

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67952

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.063
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.25
DANN	Benign	0.75
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.021
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.19
Sift	Benign	0.54	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.073
MutPred		0.11		Gain of catalytic residue at N789 (P = 0.0149)
MVP		0.43
ClinPred		0.015	T
GERP RS		-7.7
Varity_R		0.027
gMVP		0.097
Mutation Taster		=80/20	polymorphism

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

dbSNP: rs543409817; hg19: chr14-91338465;