rs375856624

Variant names:

• chr12-120200749-T-A
• NM_001002.4:c.35A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-120200749-T-A
• chr12-120200749-T-C

Variant summary

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

The NM_001002.4(RPLP0):​c.35A>T​(p.Asn12Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,306 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N12S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RPLP0 NM_001002.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.85

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 rank	MANE	Protein	UniProt
RPLP0	NM_001002.4	c.35A>T	p.Asn12Ile	missense_variant	Exon 2 of 8	ENST00000392514.9	NP_000993.1
RPLP0	NM_053275.4	c.35A>T	p.Asn12Ile	missense_variant	Exon 2 of 8		NP_444505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPLP0	ENST00000392514.9	c.35A>T	p.Asn12Ile	missense_variant	Exon 2 of 8	1	NM_001002.4	ENSP00000376299.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459306 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725764

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T;.;T;T;T;T;.;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	.;.;D;D;D;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.66	T
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-6.5	D;D;D;D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Benign	0.18	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T;T;T;.;.
Polyphen		0.83	P;P;.;.;P;.;.;.;.
Vest4		0.78
MutPred		0.45		Gain of catalytic residue at N12 (P = 0.0223);Gain of catalytic residue at N12 (P = 0.0223);Gain of catalytic residue at N12 (P = 0.0223);Gain of catalytic residue at N12 (P = 0.0223);Gain of catalytic residue at N12 (P = 0.0223);Gain of catalytic residue at N12 (P = 0.0223);Gain of catalytic residue at N12 (P = 0.0223);Gain of catalytic residue at N12 (P = 0.0223);Gain of catalytic residue at N12 (P = 0.0223);
MVP		0.49
MPC		1.2
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7
Varity_R		0.70
gMVP		0.86

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: chr12-120638552;