rs766367909

Variant names:

• chr3-23917960-C-G
• NM_002948.5:c.101C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-23917960-C-G
• chr3-23917960-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_002948.5(RPL15):​c.101C>G​(p.Ser34Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RPL15 NM_002948.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.86

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

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity RL15_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.806

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL15	NM_002948.5	c.101C>G	p.Ser34Cys	missense_variant	Exon 2 of 4	ENST00000307839.10	NP_002939.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL15	ENST00000307839.10	c.101C>G	p.Ser34Cys	missense_variant	Exon 2 of 4	1	NM_002948.5	ENSP00000309334.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461482 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727044

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

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	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;T;T;T;T;T;.;.;.;T;T;.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	.;T;T;T;.;.;T;T;T;.;.;T;.
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.8	L;.;L;.;L;L;.;L;.;L;L;.;L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.5	D;D;.;D;D;D;.;D;D;D;.;.;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.014	D;D;.;D;D;D;.;D;D;D;.;.;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;D;.;D;D;D;.;.;D
Polyphen		0.89	P;.;P;.;P;P;.;.;.;P;P;.;P
Vest4		0.78
MutPred		0.47		Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);Loss of disorder (P = 0.025);
MVP		0.59
MPC		1.5
ClinPred		0.96	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.44
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr3-23959451;