dbSNP rs910269617: RPL13:p.Arg60Ser (chr16-89561300-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000977.4(RPL13):c.178C>A(p.Arg60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPL13
NM_000977.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.503

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]

RPL13 links:

SNORD68 (HGNC:32729): (small nucleolar RNA, C/D box 68)

SNORD68 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL13	NM_000977.4 link	c.178C>A	p.Arg60Ser	missense_variant	Exon 3 of 6	ENST00000311528.10	NP_000968.2	P26373-1A8K4C8
RPL13	NM_033251.2 link	c.178C>A	p.Arg60Ser	missense_variant	Exon 2 of 5		NP_150254.1	P26373-1A8K4C8
RPL13	NM_001243131.1 link	c.178C>A	p.Arg60Ser	missense_variant	Exon 3 of 7		NP_001230060.1	P26373-2
SNORD68	NR_002450.1 link	n.-130C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL13	ENST00000311528.10 link	c.178C>A	p.Arg60Ser	missense_variant	Exon 3 of 6	1	NM_000977.4	ENSP00000307889.5		P26373-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1424110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706816

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T;.;.;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.97

.;.;D;D;D

M_CAP

Benign

0.055

MetaRNN

Pathogenic

0.81

D;D;D;D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Pathogenic

3.2

M;M;M;.;M

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-5.1

D;D;D;.;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

D;D;D;.;D

Sift4G

Uncertain

0.011

D;D;D;D;D

Polyphen

0.95

P;P;.;.;P

Vest4

0.92

MutPred

0.66

Loss of MoRF binding (P = 0.0465);Loss of MoRF binding (P = 0.0465);Loss of MoRF binding (P = 0.0465);Loss of MoRF binding (P = 0.0465);Loss of MoRF binding (P = 0.0465);

MVP

0.74

MPC

2.4

ClinPred

1.0

GERP RS

-8.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.89

gMVP

0.85

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over