chr12-120196852-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001002.4(RPLP0):c.875C>T(p.Ala292Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPLP0
NM_001002.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76

Publications

0 publications found

Variant links:

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]

RPLP0 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25883892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPLP0	NM_001002.4 link	c.875C>T	p.Ala292Val	missense_variant	Exon 8 of 8	ENST00000392514.9	NP_000993.1	P05388-1A0A024RBS2
RPLP0	NM_053275.4 link	c.875C>T	p.Ala292Val	missense_variant	Exon 8 of 8		NP_444505.1	P05388-1A0A024RBS2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPLP0	ENST00000392514.9 link	c.875C>T	p.Ala292Val	missense_variant	Exon 8 of 8	1	NM_001002.4	ENSP00000376299.4		P05388-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246122

AF XY:

0.00000746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.85e-7

AC:

AN:

1458942

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725536

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4554

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110838

Other (OTH)

AF:

0.00

AC:

AN:

60206

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.875C>T (p.A292V) alteration is located in exon 8 (coding exon 7) of the RPLP0 gene. This alteration results from a C to T substitution at nucleotide position 875, causing the alanine (A) at amino acid position 292 to be replaced by a valine (V). 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

Benign

0.14

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

T;T;T;.;T;T;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.28

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.71

.;.;T;T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.26

T;T;T;T;T;T;T

MetaSVM

Benign

-0.69

PhyloP100

5.8

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N

REVEL

Benign

0.25

Sift

Uncertain

0.014

D;D;D;D;D;D;D

Sift4G

Uncertain

0.039

D;D;D;D;D;D;T

Polyphen

0.013

B;B;.;.;.;B;.

Vest4

0.40

MutPred

0.50

Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);.;.;.;Gain of helix (P = 0.0325);.;

MVP

0.31

MPC

1.5

ClinPred

0.72

GERP RS

4.8

Varity_R

0.11

gMVP

0.52

Mutation Taster

=70/30

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over