NM_001018.5:c.140_141delGGinsAA

Variant names:

• chr19-1440069-GG-AA
• NM_001018.5:c.140_141delGGinsAA
• RPS15 p.Arg47Gln

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_001018.5(RPS15):c.140_141delGGinsAA (p.Arg47Gln) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. The affected nucleotide is highly conserved across species (PhyloP 100-way vertebrate score: 9.32). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.R47P: Benign (ClinVar VariationId 440242, 2 stars)

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS15 NM_001018.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 0 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]

RPS15 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD/XL) (threshold 0.0001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001018.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	RPS15 NM_001018.5	MANE Select	c.140_141delGGinsAA p.Arg47Gln	missense	N/A	Prot: NP_001009.1 UniProt:
	RPS15 NM_001308226.2		c.161_162delGGinsAA p.Arg54Gln	missense	N/A	Prot: NP_001295155.1 UniProt:

RPS15 NM_001018.5

MANE Select

HGVSc / HGVSpc.140_141delGGinsAAp.Arg47Gln

Exon rankN/A

missense

Prot: NP_001009.1UniProt: P62841

RPS15 NM_001308226.2

HGVSc / HGVSpc.161_162delGGinsAAp.Arg54Gln

Exon rankN/A

missense

Prot: NP_001295155.1UniProt: K7ELC2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	RPS15 ENST00000592588.7	TSL:1MANE Select	c.140_141delGGinsAA p.Arg47Gln	missense	N/A	Prot: ENSP00000467466.3 UniProt:
	RPS15 ENST00000592623.5	TSL:1	c.59_60delGGinsAA p.Arg20Gln	missense	N/A	Prot: ENSP00000474433.2 UniProt:
	RPS15 ENST00000593052.5	TSL:2	c.161_162delGGinsAA p.Arg54Gln	missense	N/A	Prot: ENSP00000466010.1 UniProt:

RPS15 ENST00000592588.7

TSL:1MANE Select

HGVSc / HGVSpc.140_141delGGinsAAp.Arg47Gln

Exon rankN/A

missense

Prot: ENSP00000467466.3UniProt: P62841

RPS15 ENST00000592623.5

TSL:1

HGVSc / HGVSpc.59_60delGGinsAAp.Arg20Gln

Exon rankN/A

missense

Prot: ENSP00000474433.2UniProt: A0A0B4J2B4

RPS15 ENST00000593052.5

TSL:2

HGVSc / HGVSpc.161_162delGGinsAAp.Arg54Gln

Exon rankN/A

missense

Prot: ENSP00000466010.1UniProt: K7ELC2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Pathogenic	9.3

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr19-1440068;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar