NM_002948.5:c.156C>G

Variant names:

• chr3-23918015-C-G
• rs749731223
• NM_002948.5:c.156C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002948.5(RPL15):​c.156C>G​(p.Gly52Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G52G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPL15 NM_002948.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.82
• Publications: 1 publications found

Genes affected

RPL15 (HGNC:10306): (ribosomal protein L15) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L15E family of ribosomal proteins and a component of the 60S subunit. This gene shares sequence similarity with the yeast ribosomal protein YL10 gene. Elevated expression of this gene has been observed in esophageal tumors and gastric cancer tissues, and deletion of this gene has been observed in a Diamond-Blackfan anemia (DBA) patient. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Mar 2017]

NKIRAS1 (HGNC:17899): (NFKB inhibitor interacting Ras like 1) Predicted to enable GTPase activating protein binding activity. Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to act upstream of or within several processes, including Ral protein signal transduction; lung alveolus development; and surfactant homeostasis. Located in cytosol and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-4.82 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002948.5. 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
	RPL15	NM_002948.5	MANE Select	c.156C>G	p.Gly52Gly	synonymous	Exon 2 of 4	NP_002939.2
	RPL15	NM_001253379.2		c.156C>G	p.Gly52Gly	synonymous	Exon 2 of 4	NP_001240308.1	P61313-1
	RPL15	NM_001253380.2		c.156C>G	p.Gly52Gly	synonymous	Exon 1 of 3	NP_001240309.1	P61313-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL15	ENST00000307839.10	TSL:1 MANE Select	c.156C>G	p.Gly52Gly	synonymous	Exon 2 of 4	ENSP00000309334.5	P61313-1
	RPL15	ENST00000354811.5	TSL:1	c.156C>G	p.Gly52Gly	synonymous	Exon 1 of 3	ENSP00000346867.5	P61313-1
	RPL15	ENST00000456530.7	TSL:1	c.156C>G	p.Gly52Gly	synonymous	Exon 2 of 5	ENSP00000398788.2	P61313-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.0
DANN	Benign	0.80
PhyloP100		-4.8
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs749731223; hg19: chr3-23959506;