chr12-120198592-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001002.4(RPLP0):ā€‹c.613G>Cā€‹(p.Asp205His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

RPLP0
NM_001002.4 missense

Scores

8
8
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.82
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.854

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPLP0NM_001002.4 linkuse as main transcriptc.613G>C p.Asp205His missense_variant 6/8 ENST00000392514.9
RPLP0NM_053275.4 linkuse as main transcriptc.613G>C p.Asp205His missense_variant 6/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPLP0ENST00000392514.9 linkuse as main transcriptc.613G>C p.Asp205His missense_variant 6/81 NM_001002.4 P1P05388-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461832
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727220
show subpopulations
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.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 07, 2022The c.613G>C (p.D205H) alteration is located in exon 6 (coding exon 5) of the RPLP0 gene. This alteration results from a G to C substitution at nucleotide position 613, causing the aspartic acid (D) at amino acid position 205 to be replaced by a histidine (H). 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
0.98
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.46
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.68
D;D;T;D;T;T;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
.;.;D;D;D;D;D
M_CAP
Benign
0.045
D
MetaRNN
Pathogenic
0.85
D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.11
T
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-6.3
D;D;D;D;D;D;D
REVEL
Pathogenic
0.79
Sift
Pathogenic
0.0
D;D;D;D;D;D;D
Sift4G
Uncertain
0.023
D;D;D;D;D;D;.
Polyphen
0.38
B;B;.;B;.;.;.
Vest4
0.92
MutPred
0.54
Gain of catalytic residue at L204 (P = 6e-04);Gain of catalytic residue at L204 (P = 6e-04);.;Gain of catalytic residue at L204 (P = 6e-04);.;.;Gain of catalytic residue at L204 (P = 6e-04);
MVP
0.80
MPC
1.0
ClinPred
1.0
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.91
gMVP
0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-120636395; API