12-120196864-G-A

Variant names:

• chr12-120196864-G-A
• rs746667978
• NM_001002.4:c.863C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001002.4(RPLP0):​c.863C>T​(p.Ala288Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,459,902 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. A288D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: RPLP0 NM_001002.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.32
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 39 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPLP0	NM_001002.4	MANE Select	c.863C>T	p.Ala288Val	missense	Exon 8 of 8	NP_000993.1	P05388-1
	RPLP0	NM_053275.4		c.863C>T	p.Ala288Val	missense	Exon 8 of 8	NP_444505.1	P05388-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPLP0	ENST00000392514.9	TSL:1 MANE Select	c.863C>T	p.Ala288Val	missense	Exon 8 of 8	ENSP00000376299.4	P05388-1
	RPLP0	ENST00000228306.8	TSL:1	c.863C>T	p.Ala288Val	missense	Exon 8 of 8	ENSP00000339027.3	P05388-1
	RPLP0	ENST00000551150.5	TSL:1	c.863C>T	p.Ala288Val	missense	Exon 7 of 7	ENSP00000449328.1	P05388-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1459902 Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26 AN XY: 726170

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4704

European-Non Finnish (NFE) AF: 0.0000342 AC: 38 AN: 1111558

Other (OTH) AF: 0.00 AC: 0 AN: 60256

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.59	D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	-0.010	T
PhyloP100		7.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.32
Sift	Benign	0.032	D
Sift4G	Uncertain	0.049	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.56		Gain of catalytic residue at T285 (P = 0.0024)
MVP		0.41
MPC		1.0
ClinPred		0.89	D
GERP RS		5.7
Varity_R		0.19
gMVP		0.64
Mutation Taster		=44/56	disease causing

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

Other links and lift over

dbSNP: rs746667978; hg19: chr12-120634667;