Genetic Variant RPL29:p.Pro83Ser (chr3-51993982-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000992.3(RPL29):c.247C>T(p.Pro83Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,597,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RPL29
NM_000992.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.602

Variant links:

Genes affected

RPL29 (HGNC:10331): (ribosomal protein L29) 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 cytoplasmic ribosomal protein that is a component of the 60S subunit. The protein belongs to the L29E family of ribosomal proteins. The protein is also a peripheral membrane protein expressed on the cell surface that directly binds heparin. Although this gene was previously reported to map to 3q29-qter, it is believed that it is located at 3p21.3-p21.2. 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]

RPL29 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17299068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL29	NM_000992.3 link	c.247C>T	p.Pro83Ser	missense_variant	Exon 4 of 4	ENST00000294189.11	NP_000983.1	P47914

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL29	ENST00000294189.11 link	c.247C>T	p.Pro83Ser	missense_variant	Exon 4 of 4	1	NM_000992.3	ENSP00000294189.4		P47914

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1445208

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719362

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.247C>T (p.P83S) alteration is located in exon 4 (coding exon 3) of the RPL29 gene. This alteration results from a C to T substitution at nucleotide position 247, causing the proline (P) at amino acid position 83 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Pathogenic

0.80

.;D;D;D;D;D;D

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.73

T;.;.;.;.;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.17

T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

2.9

.;M;M;M;M;M;M

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-6.2

.;D;D;D;D;D;D

REVEL

Benign

0.19

Sift

Benign

0.057

.;T;T;T;T;T;T

Sift4G

Benign

0.073

.;T;T;T;T;T;.

Polyphen

0.19

.;B;B;B;B;B;B

Vest4

0.46, 0.41, 0.46, 0.46

MutPred

0.38

.;Loss of glycosylation at K87 (P = 0.0435);Loss of glycosylation at K87 (P = 0.0435);Loss of glycosylation at K87 (P = 0.0435);Loss of glycosylation at K87 (P = 0.0435);Loss of glycosylation at K87 (P = 0.0435);Loss of glycosylation at K87 (P = 0.0435);

MVP

0.55

MPC

1.3

ClinPred

0.41

GERP RS

1.7

Varity_R

0.22

gMVP

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over