chr14-90869843-T-C

Variant names:

• chr14-90869843-T-C
• rs8018757
• NM_004755.4:c.*2231A>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.*2231A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,768 control chromosomes in the GnomAD database, including 26,529 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 0.59 (26529 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: RPS6KA5 NM_004755.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 0 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 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.*2231A>G		3_prime_UTR	Exon 17 of 17	NP_004746.2
	RPS6KA5	NM_001322229.2		c.*2231A>G		3_prime_UTR	Exon 17 of 17	NP_001309158.1
	RPS6KA5	NM_001322236.2		c.*2231A>G		3_prime_UTR	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.*2231A>G		3_prime_UTR	Exon 17 of 17	ENSP00000479667.1	O75582-1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 88994 AN: 151650 Hom.: 26491 Cov.: 30

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.600

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.587 AC: 89095 AN: 151768 Hom.: 26529 Cov.: 30 AF XY: 0.586 AC XY: 43449 AN XY: 74192

African (AFR) AF: 0.688 AC: 28497 AN: 41402

American (AMR) AF: 0.560 AC: 8544 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1904 AN: 3454

East Asian (EAS) AF: 0.630 AC: 3245 AN: 5152

South Asian (SAS) AF: 0.600 AC: 2880 AN: 4804

European-Finnish (FIN) AF: 0.517 AC: 5441 AN: 10530

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36669 AN: 67872

Other (OTH) AF: 0.600 AC: 1264 AN: 2108

Alfa AF: 0.551 Hom.: 4754

Bravo AF: 0.592

Asia WGS AF: 0.633 AC: 2199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.092
DANN	Benign	0.35
PhyloP100		-2.1

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: rs8018757; hg19: chr14-91336187;