chr3-23917859-G-C

Variant names:

• chr3-23917859-G-C
• rs567287618
• NM_002948.5:c.-1G>C

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+1 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 1 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Supporting

The NM_002948.5(RPL15):c.-1G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The gene RPL15 is a tumor suppressor gene (CancerMine: 1 TSG citations). The variant allele was found at a cumulative frequency of 0.0000591 (AC=9) in the gnomAD database across 152,352 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000954. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPL15 NM_002948.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.436
• Publications: 0 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]

RPL15 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 12

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NKIRAS1 (HGNC:17899): (NFKB inhibitor interacting Ras like 1) Predicted to enable GTPase activating protein binding activity. Predicted to be involved in Ral protein signal transduction. Predicted to act upstream of or within lung alveolus development; regulation of tumor necrosis factor-mediated signaling pathway; and surfactant homeostasis. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Very rare in gnomAD (popmax AF <0.01%) — O3 supporting; GnomAD effective popmax AF = 0.000095 — very rare (O3 supporting [+1])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002948.5. 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
	RPL15 NM_002948.5	MANE Select	c.-1G>C	5_prime_UTR	Exon 2 of 4	Prot: NP_002939.2
	RPL15 NM_001253379.2		c.-1G>C	5_prime_UTR	Exon 2 of 4	Prot: NP_001240308.1 UniProt:
	RPL15 NM_001253380.2		c.-1G>C	5_prime_UTR	Exon 1 of 3	Prot: NP_001240309.1 UniProt:

RPL15 NM_002948.5

MANE Select

HGVSc / HGVSpc.-1G>C

Exon rankExon 2 of 4

5_prime_UTR

Prot: NP_002939.2

RPL15 NM_001253379.2

HGVSc / HGVSpc.-1G>C

Exon rankExon 2 of 4

5_prime_UTR

Prot: NP_001240308.1UniProt: P61313-1

RPL15 NM_001253380.2

HGVSc / HGVSpc.-1G>C

Exon rankExon 1 of 3

5_prime_UTR

Prot: NP_001240309.1UniProt: P61313-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	RPL15 ENST00000307839.10	TSL:1MANE Select	c.-1G>C	5_prime_UTR	Exon 2 of 4	Prot: ENSP00000309334.5 UniProt:
	RPL15 ENST00000354811.5	TSL:1	c.-1G>C	5_prime_UTR	Exon 1 of 3	Prot: ENSP00000346867.5 UniProt:
	RPL15 ENST00000456530.7	TSL:1	c.-1G>C	5_prime_UTR	Exon 2 of 5	Prot: ENSP00000398788.2 UniProt:

RPL15 ENST00000307839.10

TSL:1MANE Select

HGVSc / HGVSpc.-1G>C

Exon rankExon 2 of 4

5_prime_UTR

Prot: ENSP00000309334.5UniProt: P61313-1

RPL15 ENST00000354811.5

TSL:1

HGVSc / HGVSpc.-1G>C

Exon rankExon 1 of 3

5_prime_UTR

Prot: ENSP00000346867.5UniProt: P61313-1

RPL15 ENST00000456530.7

TSL:1

HGVSc / HGVSpc.-1G>C

Exon rankExon 2 of 5

5_prime_UTR

Prot: ENSP00000398788.2UniProt: P61313-2

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 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.0000591	AC:9	Hom:0	AN:152234	Cov:33
GnomAD2 exomes	AF: 0.00000407	AC:1	Hom:	AN:245526	Cov:
GnomAD4 exome Warning	AF: 0.00000275	AC:4	Hom:0	AN:1455800	Cov:31
GnomAD4 genome	AF: 0.0000591	AC:9	Hom:0	AN:152352	Cov:33
TOPMed (Bravo)	AF: 0.0000227	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.0000509	AC:1	Hom:0	AN:19650	Cov:

Showing 6 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.0000520	3	57640	0.0000251	2	79568

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	18
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.90
GPN-Star LLR	N/A	-3.5
GPN-Star score	N/A	3.5
PhyloP100	Benign	0.44
PromoterAI	N/A	-0.0076	Neutral
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.7

Showing 10 of 10 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.030
SpliceAI score (max)	Benign	0.040	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

dbSNP: rs567287618;

hg19: chr3-23959350;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar