NM_004755.4:c.510+1018G>C

Variant names:

• chr14-90946417-C-G
• rs1286112
• NM_004755.4:c.510+1018G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004755.4(RPS6KA5):​c.510+1018G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 151,928 control chromosomes in the GnomAD database, including 40,751 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (40751 hom., cov: 30)
• Consequence: RPS6KA5 NM_004755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

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.510+1018G>C		intron	N/A	NP_004746.2
	RPS6KA5	NM_001322229.2		c.510+1018G>C		intron	N/A	NP_001309158.1
	RPS6KA5	NM_001322236.2		c.510+1018G>C		intron	N/A	NP_001309165.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA5	ENST00000614987.5	TSL:1 MANE Select	c.510+1018G>C		intron	N/A	ENSP00000479667.1	O75582-1
	RPS6KA5	ENST00000418736.6	TSL:1	c.510+1018G>C		intron	N/A	ENSP00000402787.2	O75582-2
	RPS6KA5	ENST00000554206.1	TSL:1	n.510+1018G>C		intron	N/A	ENSP00000450591.1	G3V2D1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 110958 AN: 151810 Hom.: 40719 Cov.: 30

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.719

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.731 AC: 111034 AN: 151928 Hom.: 40751 Cov.: 30 AF XY: 0.733 AC XY: 54420 AN XY: 74228

African (AFR) AF: 0.705 AC: 29166 AN: 41398

American (AMR) AF: 0.722 AC: 11020 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3468

East Asian (EAS) AF: 0.967 AC: 5000 AN: 5168

South Asian (SAS) AF: 0.772 AC: 3708 AN: 4802

European-Finnish (FIN) AF: 0.757 AC: 7986 AN: 10548

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.729 AC: 49524 AN: 67962

Other (OTH) AF: 0.722 AC: 1524 AN: 2112

Alfa AF: 0.736 Hom.: 4826

Bravo AF: 0.727

Asia WGS AF: 0.856 AC: 2976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.42
PhyloP100		-0.018
Mutation Taster		=100/0	polymorphism (auto)

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: rs1286112; hg19: chr14-91412761;