rs3783833

Variant names:

• chr14-90969246-T-C
• rs3783833
• NM_004755.4:c.394+9060A>G

Variant summary

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

The NM_004755.4(RPS6KA5):​c.394+9060A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,202 control chromosomes in the GnomAD database, including 2,438 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 0.17 (2438 hom., cov: 32)
• Consequence: RPS6KA5 NM_004755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA5	NM_004755.4	c.394+9060A>G		intron_variant	Intron 3 of 16	ENST00000614987.5	NP_004746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA5	ENST00000614987.5	c.394+9060A>G		intron_variant	Intron 3 of 16	1	NM_004755.4	ENSP00000479667.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25571 AN: 152084 Hom.: 2431 Cov.: 32

Gnomad AFR AF: 0.0977

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.168 AC: 25614 AN: 152202 Hom.: 2438 Cov.: 32 AF XY: 0.168 AC XY: 12488 AN XY: 74406

African (AFR) AF: 0.0981 AC: 4075 AN: 41560

American (AMR) AF: 0.166 AC: 2542 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 959 AN: 3468

East Asian (EAS) AF: 0.324 AC: 1676 AN: 5178

South Asian (SAS) AF: 0.197 AC: 948 AN: 4824

European-Finnish (FIN) AF: 0.138 AC: 1461 AN: 10582

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13333 AN: 67976

Other (OTH) AF: 0.200 AC: 422 AN: 2114

Alfa AF: 0.198 Hom.: 5009

Bravo AF: 0.169

Asia WGS AF: 0.301 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.29
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: rs3783833; hg19: chr14-91435590;