3-51994081-T-C

Position:

• chr3-51994081-T-C

Variant summary

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

The ENST00000294189.11(RPL29):​c.148A>G​(p.Asn50Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,451,732 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPL29 ENST00000294189.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL29	NM_000992.3	c.148A>G	p.Asn50Asp	missense_variant	4/4	ENST00000294189.11	NP_000983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL29	ENST00000294189.11	c.148A>G	p.Asn50Asp	missense_variant	4/4	1	NM_000992.3	ENSP00000294189	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451732 Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2 AN XY: 721704

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000449

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.148A>G (p.N50D) alteration is located in exon 4 (coding exon 3) of the RPL29 gene. This alteration results from a A to G substitution at nucleotide position 148, causing the asparagine (N) at amino acid position 50 to be replaced by an aspartic acid (D). 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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	.;D;D;D;D;D;D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T;.;.;.;.;.;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Pathogenic	3.6	.;H;H;H;H;H;H
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.1	.;D;D;D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.028	.;D;D;D;D;D;D
Sift4G	Uncertain	0.040	.;D;D;D;D;D;.
Polyphen		0.77	.;P;P;P;P;P;P
Vest4		0.79, 0.79, 0.79
MutPred		0.33		.;Loss of glycosylation at K52 (P = 0.038);Loss of glycosylation at K52 (P = 0.038);Loss of glycosylation at K52 (P = 0.038);Loss of glycosylation at K52 (P = 0.038);Loss of glycosylation at K52 (P = 0.038);Loss of glycosylation at K52 (P = 0.038);
MVP		0.55
MPC		1.3
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.72
gMVP		0.48

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: rs1353158560; hg19: chr3-52028097;