rs201657403

Variant names:

• chr19-1440069-G-A
• rs201657403
• NM_001018.5:c.140G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-1440069-G-A
• chr19-1440069-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001308226.2(RPS15):​c.161G>A​(p.Arg54Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,425,242 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R54P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: RPS15 NM_001308226.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 15 publications found

Genes affected

RPS15 (HGNC:10388): (ribosomal protein S15) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S19P family of ribosomal proteins. It is located in the cytoplasm. This gene has been found to be activated in various tumors, such as insulinomas, esophageal cancers, and colon cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 21 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308226.2. 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
	RPS15	NM_001018.5	MANE Select	c.140G>A	p.Arg47Gln	missense	Exon 3 of 4	NP_001009.1
	RPS15	NM_001308226.2		c.161G>A	p.Arg54Gln	missense	Exon 3 of 4	NP_001295155.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS15	ENST00000592588.7	TSL:1 MANE Select	c.140G>A	p.Arg47Gln	missense	Exon 3 of 4	ENSP00000467466.3
	RPS15	ENST00000592623.5	TSL:1	c.59G>A	p.Arg20Gln	missense	Exon 2 of 3	ENSP00000474433.2
	RPS15	ENST00000593052.5	TSL:2	c.161G>A	p.Arg54Gln	missense	Exon 3 of 4	ENSP00000466010.1

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150832 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 2 AN: 123918 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000206

Gnomad OTH exome AF: 0.000277

GnomAD4 exome AF: 0.0000165 AC: 21 AN: 1274410 Hom.: 0 Cov.: 37 AF XY: 0.0000142 AC XY: 9 AN XY: 632106

African (AFR) AF: 0.0000336 AC: 1 AN: 29802

American (AMR) AF: 0.0000294 AC: 1 AN: 33988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23650

East Asian (EAS) AF: 0.00 AC: 0 AN: 36704

South Asian (SAS) AF: 0.00 AC: 0 AN: 75542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4238

European-Non Finnish (NFE) AF: 0.0000196 AC: 19 AN: 971140

Other (OTH) AF: 0.00 AC: 0 AN: 53864

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150832 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73614

African (AFR) AF: 0.00 AC: 0 AN: 41158

American (AMR) AF: 0.0000661 AC: 1 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67450

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.035
Eigen_PC	Benign	-0.027
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		9.3
PrimateAI	Pathogenic	0.84	D
REVEL	Uncertain	0.32
Sift4G	Uncertain	0.041	D
Polyphen		0.32	B
Vest4		0.72
MutPred		0.70		Loss of methylation at R47 (P = 0.0349)
MVP		0.85
MPC		1.6
ClinPred		0.89	D
GERP RS		3.2
Varity_R		0.88
gMVP		0.97
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201657403; hg19: chr19-1440068;