12-120199133-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001002.4(RPLP0):c.303G>A(p.Met101Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RPLP0 NM_001002.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29164642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPLP0	NM_001002.4	c.303G>A	p.Met101Ile	missense_variant	4/8	ENST00000392514.9
RPLP0	NM_053275.4	c.303G>A	p.Met101Ile	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPLP0	ENST00000392514.9	c.303G>A	p.Met101Ile	missense_variant	4/8	1	NM_001002.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461438 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727054

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: 9.00e-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:

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.303G>A (p.M101I) alteration is located in exon 4 (coding exon 3) of the RPLP0 gene. This alteration results from a G to A substitution at nucleotide position 303, causing the methionine (M) at amino acid position 101 to be replaced by an isoleucine (I). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.020

T

BayesDel_noAF

Benign

-0.27

Cadd

Uncertain

24

Dann

Uncertain

0.98

DEOGEN2

Benign

0.11

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

Eigen

Benign

-0.10

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

D

M_CAP

Benign

0.0057

T

MetaRNN

Benign

0.29

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

MetaSVM

Benign

-1.1

T

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.78

T

PROVEAN

Benign

-0.99

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

REVEL

Benign

0.19

Sift

Benign

0.23

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

Sift4G

Benign

0.23

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

Polyphen

0.0010

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

Vest4

0.60

MutPred

0.46

Gain of catalytic residue at L102 (P = 0.0015);Gain of catalytic residue at L102 (P = 0.0015);Gain of catalytic residue at L102 (P = 0.0015);Gain of catalytic residue at L102 (P = 0.0015);Gain of catalytic residue at L102 (P = 0.0015);Gain of catalytic residue at L102 (P = 0.0015);.;Gain of catalytic residue at L102 (P = 0.0015);.;.;Gain of catalytic residue at L102 (P = 0.0015);

MVP

0.53

MPC

0.76

ClinPred

0.79

D

GERP RS

5.3

Varity_R

0.24

gMVP

0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-120636936;