Genetic Variant NM_001032.5:c.139G>A (chr14-49585973-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

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

The NM_001032.5(RPS29):c.139G>A(p.Ala47Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,488 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 6.8e-7 ( 0 hom. )

Consequence

RPS29
NM_001032.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.40

Variant links:

Genes affected

RPS29 (HGNC:10419): (ribosomal protein S29) 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 40S subunit and a member of the S14P family of ribosomal proteins. The protein, which contains a C2-C2 zinc finger-like domain that can bind to zinc, can enhance the tumor suppressor activity of Ras-related protein 1A (KREV1). It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

RPS29 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, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS29	NM_001032.5 link	c.139G>A	p.Ala47Thr	missense_variant	Exon 2 of 3	ENST00000245458.11	NP_001023.1	P62273-1
RPS29	NM_001030001.4 link	c.139G>A	p.Ala47Thr	missense_variant	Exon 2 of 3		NP_001025172.1	P62273-2
RPS29	NM_001351375.2 link	c.130G>A	p.Ala44Thr	missense_variant	Exon 2 of 3		NP_001338304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS29	ENST00000245458.11 link	c.139G>A	p.Ala47Thr	missense_variant	Exon 2 of 3	1	NM_001032.5	ENSP00000245458.7		P62273-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461488

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727072

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.86

.;D;D;T;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

D;.;D;D;D;D

M_CAP

Pathogenic

0.31

MetaRNN

Pathogenic

0.83

D;D;D;D;D;D

MetaSVM

Benign

-0.73

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.3

D;D;.;.;.;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.025

D;D;.;.;.;.

Sift4G

Uncertain

0.024

D;D;.;D;.;.

Polyphen

0.040

.;B;B;.;.;.

Vest4

0.90

MutPred

0.70

Gain of catalytic residue at Q45 (P = 0.0019);Gain of catalytic residue at Q45 (P = 0.0019);Gain of catalytic residue at Q45 (P = 0.0019);.;Gain of catalytic residue at Q45 (P = 0.0019);.;

MVP

0.30

MPC

2.4

ClinPred

1.0

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.87

gMVP

0.95

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over