rs7155799

Positions:

• chr14-90869968-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004755.4(RPS6KA5):​c.*2106G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,074 control chromosomes in the GnomAD database, including 3,332 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 0.21 (3332 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RPS6KA5 NM_004755.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA5	NM_004755.4	c.*2106G>A		3_prime_UTR_variant	17/17	ENST00000614987.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA5	ENST00000614987.5	c.*2106G>A		3_prime_UTR_variant	17/17	1	NM_004755.4	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31335 AN: 151956 Hom.: 3323 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.225

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.206 AC: 31380 AN: 152074 Hom.: 3332 Cov.: 32 AF XY: 0.204 AC XY: 15144 AN XY: 74334

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.228

Alfa AF: 0.232 Hom.: 7056

Bravo AF: 0.206

Asia WGS AF: 0.254 AC: 882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
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: rs7155799; hg19: chr14-91336312;