16-89562959-G-C

Variant names:

• chr16-89562959-G-C
• rs2058757423
• NM_000977.4:c.553G>C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.88

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]

ACMG classification

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
RPL13	NM_000977.4	c.553G>C	p.Ala185Pro	missense_variant	Exon 6 of 6	ENST00000311528.10	NP_000968.2
RPL13	NM_033251.2	c.553G>C	p.Ala185Pro	missense_variant	Exon 5 of 5		NP_150254.1
RPL13	NM_001243131.1	c.412G>C	p.Ala138Pro	missense_variant	Exon 7 of 7		NP_001230060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL13	ENST00000311528.10	c.553G>C	p.Ala185Pro	missense_variant	Exon 6 of 6	1	NM_000977.4	ENSP00000307889.5

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

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

Other links and lift over

dbSNP: rs2058757423; hg19: chr16-89629367;