3-51993870-C-G

Variant names:

• chr3-51993870-C-G
• rs139597551
• NM_000992.3:c.359G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000992.3(RPL29):​c.359G>C​(p.Arg120Pro) 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 benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R120Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL29 NM_000992.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

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]

ACMG classification

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=0.20064017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL29	NM_000992.3	c.359G>C	p.Arg120Pro	missense_variant	Exon 4 of 4	ENST00000294189.11	NP_000983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL29	ENST00000294189.11	c.359G>C	p.Arg120Pro	missense_variant	Exon 4 of 4	1	NM_000992.3	ENSP00000294189.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000430 AC: 1 AN: 232806 Hom.: 0 AF XY: 0.00000781 AC XY: 1 AN XY: 128110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.359G>C (p.R120P) alteration is located in exon 4 (coding exon 3) of the RPL29 gene. This alteration results from a G to C substitution at nucleotide position 359, causing the arginine (R) at amino acid position 120 to be replaced by a proline (P). 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	0.21
BayesDel_addAF	Benign	-0.0031	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.69	.;D;D;D;D;D;D
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.32	T;.;.;.;.;.;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	.;M;M;M;M;M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	.;N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.12	.;T;T;T;T;T;T
Sift4G	Benign	0.11	.;T;T;T;T;T;.
Polyphen		0.80	.;P;P;P;P;P;P
Vest4		0.59, 0.59, 0.59
MutPred		0.29		.;Loss of glycosylation at P121 (P = 0.0093);Loss of glycosylation at P121 (P = 0.0093);Loss of glycosylation at P121 (P = 0.0093);Loss of glycosylation at P121 (P = 0.0093);Loss of glycosylation at P121 (P = 0.0093);Loss of glycosylation at P121 (P = 0.0093);
MVP		0.59
MPC		2.5
ClinPred		0.43	T
GERP RS		1.3
Varity_R		0.31
gMVP		0.12

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: rs139597551; hg19: chr3-52027886;