14-90946417-C-G

Position:

• chr14-90946417-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA5	NM_004755.4	c.510+1018G>C		intron_variant		ENST00000614987.5	NP_004746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA5	ENST00000614987.5	c.510+1018G>C		intron_variant		1	NM_004755.4	ENSP00000479667.1

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

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.722

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs1286112; hg19: chr14-91412761;