16-89562959-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_000977.4(RPL13):​c.553G>C​(p.Ala185Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

RPL13
NM_000977.4 missense

Scores

7
8
4

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.88
Variant links:
Genes affected
RPL13 (HGNC:10303): (ribosomal protein L13) 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 belongs to the L13E family of ribosomal proteins. It is located in the cytoplasm. This gene is expressed at significantly higher levels in benign breast lesions than in breast carcinomas. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.852
PP5
Variant 16-89562959-G-C is Pathogenic according to our data. Variant chr16-89562959-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 813854.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPL13NM_000977.4 linkc.553G>C p.Ala185Pro missense_variant Exon 6 of 6 ENST00000311528.10 NP_000968.2 P26373-1A8K4C8
RPL13NM_033251.2 linkc.553G>C p.Ala185Pro missense_variant Exon 5 of 5 NP_150254.1 P26373-1A8K4C8
RPL13NM_001243131.1 linkc.412G>C p.Ala138Pro missense_variant Exon 7 of 7 NP_001230060.1 P26373-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPL13ENST00000311528.10 linkc.553G>C p.Ala185Pro missense_variant Exon 6 of 6 1 NM_000977.4 ENSP00000307889.5 P26373-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Spondyloepimetaphyseal dysplasia, Isidor-Toutain type Pathogenic:1
Dec 15, 2019
Center for Molecular Medicine, Karolinska Institute
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T;T;T;.;T
Eigen
Pathogenic
0.74
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
.;D;.;D;D
M_CAP
Benign
0.073
D
MetaRNN
Pathogenic
0.85
D;D;D;D;D
MetaSVM
Benign
-0.34
T
MutationAssessor
Uncertain
2.9
M;.;M;.;M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-4.0
D;D;D;D;D
REVEL
Uncertain
0.62
Sift
Uncertain
0.0070
D;D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D;D
Polyphen
0.97
D;.;D;.;D
Vest4
0.89
MutPred
0.67
Loss of methylation at R186 (P = 0.1009);.;Loss of methylation at R186 (P = 0.1009);.;Loss of methylation at R186 (P = 0.1009);
MVP
0.85
MPC
0.93
ClinPred
1.0
D
GERP RS
3.6
Varity_R
0.95
gMVP
0.79

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2058757423; hg19: chr16-89629367; API