19-1440050-CAG-AGA

Variant names:

• chr19-1440050-CAG-AGA
• NM_001018.5:c.121_123delCAGinsAGA
• RPS15 p.Gln41Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001018.5(RPS15):​c.121_123delCAGinsAGA​(p.Gln41Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. Q41P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS15 NM_001018.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.75
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018.5. 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.121_123delCAGinsAGA	p.Gln41Arg	missense	N/A	NP_001009.1	P62841
	RPS15	NM_001308226.2		c.142_144delCAGinsAGA	p.Gln48Arg	missense	N/A	NP_001295155.1	K7ELC2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS15	ENST00000592588.7	TSL:1 MANE Select	c.121_123delCAGinsAGA	p.Gln41Arg	missense	N/A	ENSP00000467466.3	P62841
	RPS15	ENST00000592623.5	TSL:1	c.40_42delCAGinsAGA	p.Gln14Arg	missense	N/A	ENSP00000474433.2	A0A0B4J2B4
	RPS15	ENST00000593052.5	TSL:2	c.142_144delCAGinsAGA	p.Gln48Arg	missense	N/A	ENSP00000466010.1	K7ELC2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.8

Splicing

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.

Other links and lift over

hg19: chr19-1440049;