NM_001002.4:c.536A>C

Variant names:

• chr12-120198669-T-G
• rs776598806
• NM_001002.4:c.536A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001002.4(RPLP0):​c.536A>C​(p.Asn179Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N179S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPLP0 NM_001002.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.94
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPLP0	NM_001002.4	c.536A>C	p.Asn179Thr	missense_variant	Exon 6 of 8	ENST00000392514.9	NP_000993.1
RPLP0	NM_053275.4	c.536A>C	p.Asn179Thr	missense_variant	Exon 6 of 8		NP_444505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPLP0	ENST00000392514.9	c.536A>C	p.Asn179Thr	missense_variant	Exon 6 of 8	1	NM_001002.4	ENSP00000376299.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D;D;D;T;T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	.;.;D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.65	D;D;D;D;D;D
MetaSVM	Uncertain	-0.037	T
PhyloP100		7.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.2	D;D;D;D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0050	D;D;D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D;D;.
Polyphen		0.40	B;B;B;.;.;.
Vest4		0.84
MutPred		0.50		Gain of catalytic residue at P182 (P = 0.0011);Gain of catalytic residue at P182 (P = 0.0011);Gain of catalytic residue at P182 (P = 0.0011);.;.;Gain of catalytic residue at P182 (P = 0.0011);
MVP		0.51
MPC		0.89
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.70
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs776598806; hg19: chr12-120636472;