12-120196864-G-T

Position:

• chr12-120196864-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001002.4(RPLP0):​c.863C>A​(p.Ala288Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPLP0 NM_001002.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.32

Genes affected

RPLP0 (HGNC:10371): (ribosomal protein lateral stalk subunit P0) 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 60S subunit. The protein, which is the functional equivalent of the E. coli L10 ribosomal protein, belongs to the L10P family of ribosomal proteins. It is a neutral phosphoprotein with a C-terminal end that is nearly identical to the C-terminal ends of the acidic ribosomal phosphoproteins P1 and P2. The P0 protein can interact with P1 and P2 to form a pentameric complex consisting of P1 and P2 dimers, and a P0 monomer. The protein is located in the cytoplasm. Transcript variants derived from alternative splicing exist; they encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPLP0	NM_001002.4	c.863C>A	p.Ala288Asp	missense_variant	8/8	ENST00000392514.9	NP_000993.1
RPLP0	NM_053275.4	c.863C>A	p.Ala288Asp	missense_variant	8/8		NP_444505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPLP0	ENST00000392514.9	c.863C>A	p.Ala288Asp	missense_variant	8/8	1	NM_001002.4	ENSP00000376299	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000833 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.863C>A (p.A288D) alteration is located in exon 8 (coding exon 7) of the RPLP0 gene. This alteration results from a C to A substitution at nucleotide position 863, causing the alanine (A) at amino acid position 288 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T;T;T;.;T;T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	.;.;T;T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.60	D;D;D;D;D;D;D
MetaSVM	Benign	-0.33	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.063	T;T;T;T;T;T;D
Sift4G	Uncertain	0.024	D;D;D;D;D;D;D
Polyphen		1.0	D;D;.;.;.;D;.
Vest4		0.55
MutPred		0.55		Gain of catalytic residue at T285 (P = 0.003);Gain of catalytic residue at T285 (P = 0.003);.;.;.;Gain of catalytic residue at T285 (P = 0.003);.;
MVP		0.36
MPC		1.4
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.27
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs746667978; hg19: chr12-120634667;