12-120199160-C-T

Variant names:

• chr12-120199160-C-T
• rs148524502
• NM_001002.4:c.276G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001002.4(RPLP0):​c.276G>A​(p.Lys92Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.00924 in 1,614,064 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0096 (96 hom.)
• Consequence: RPLP0 NM_001002.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.99

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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 12-120199160-C-T is Benign according to our data. Variant chr12-120199160-C-T is described in ClinVar as [Benign]. Clinvar id is 770414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 880 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPLP0	NM_001002.4	c.276G>A	p.Lys92Lys	synonymous_variant	Exon 4 of 8	ENST00000392514.9	NP_000993.1
RPLP0	NM_053275.4	c.276G>A	p.Lys92Lys	synonymous_variant	Exon 4 of 8		NP_444505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPLP0	ENST00000392514.9	c.276G>A	p.Lys92Lys	synonymous_variant	Exon 4 of 8	1	NM_001002.4	ENSP00000376299.4

Frequencies

GnomAD3 genomes AF: 0.00578 AC: 880 AN: 152192 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00645 AC: 1621 AN: 251480 AF XY: 0.00658

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00416

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.00635

GnomAD4 exome AF: 0.00960 AC: 14030 AN: 1461754 Hom.: 96 Cov.: 32 AF XY: 0.00929 AC XY: 6755 AN XY: 727186

Gnomad4 AFR exome AF: 0.00119 AC: 40 AN: 33480

Gnomad4 AMR exome AF: 0.00277 AC: 124 AN: 44724

Gnomad4 ASJ exome AF: 0.000153 AC: 4 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.00235 AC: 203 AN: 86258

Gnomad4 FIN exome AF: 0.00425 AC: 227 AN: 53420

Gnomad4 NFE exome AF: 0.0117 AC: 12967 AN: 1111878

Gnomad4 Remaining exome AF: 0.00730 AC: 441 AN: 60390

GnomAD4 genome AF: 0.00578 AC: 880 AN: 152310 Hom.: 4 Cov.: 32 AF XY: 0.00498 AC XY: 371 AN XY: 74484

Gnomad4 AFR AF: 0.00183 AC: 0.00182824 AN: 0.00182824

Gnomad4 AMR AF: 0.00255 AC: 0.00254935 AN: 0.00254935

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00332 AC: 0.00331538 AN: 0.00331538

Gnomad4 FIN AF: 0.00358 AC: 0.00357815 AN: 0.00357815

Gnomad4 NFE AF: 0.0102 AC: 0.0102482 AN: 0.0102482

Gnomad4 OTH AF: 0.00615 AC: 0.00614948 AN: 0.00614948

Alfa AF: 0.00874 Hom.: 3

Bravo AF: 0.00569

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00911

EpiControl AF: 0.0102

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	12
DANN	Benign	0.90
Mutation Taster		=48/52	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

Publications

LitVar

Other links and lift over

dbSNP: rs148524502; hg19: chr12-120636963; COSMIC: COSV56106507; COSMIC: COSV56106507;