19-1440051-A-G

Variant names:

• chr19-1440051-A-G
• NM_001018.5:c.122A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001018.5(RPS15):​c.122A>G​(p.Gln41Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000427 in 1,406,022 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: RPS15 NM_001018.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.75

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS15	NM_001018.5	c.122A>G	p.Gln41Arg	missense_variant	Exon 3 of 4	ENST00000592588.7	NP_001009.1
RPS15	NM_001308226.2	c.143A>G	p.Gln48Arg	missense_variant	Exon 3 of 4		NP_001295155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS15	ENST00000592588.7	c.122A>G	p.Gln41Arg	missense_variant	Exon 3 of 4	1	NM_001018.5	ENSP00000467466.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000427 AC: 6 AN: 1406022 Hom.: 0 Cov.: 30 AF XY: 0.00000288 AC XY: 2 AN XY: 694118

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000278

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000270

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000369

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.026	T;.;T;.;T;.;.;.;T;T;.
Eigen	Benign	0.035
Eigen_PC	Benign	0.071
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	.;.;T;T;T;T;T;.;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	2.0	.;.;M;.;.;.;.;.;.;.;.
PrimateAI	Pathogenic	0.85	D
REVEL	Benign	0.29
Sift4G	Benign	0.34	T;T;T;.;T;T;T;T;T;T;T
Polyphen		0.0010	.;.;B;.;.;.;.;.;.;.;.
Vest4		0.74
MutPred		0.26		.;.;Gain of methylation at Q41 (P = 0.0231);.;.;.;Gain of methylation at Q41 (P = 0.0231);.;.;Gain of methylation at Q41 (P = 0.0231);.;
MVP		0.85
MPC		1.4
ClinPred		0.89	D
GERP RS		4.3
Varity_R		0.55
gMVP		0.96

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1440050;