chr3-51994040-C-G

Variant names:

• chr3-51994040-C-G
• rs754547606
• NM_000992.3:c.189G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000992.3(RPL29):​c.189G>C​(p.Lys63Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPL29 NM_000992.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28293687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000992.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL29	NM_000992.3	MANE Select	c.189G>C	p.Lys63Asn	missense	Exon 4 of 4	NP_000983.1	P47914

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL29	ENST00000294189.11	TSL:1 MANE Select	c.189G>C	p.Lys63Asn	missense	Exon 4 of 4	ENSP00000294189.4	P47914
	RPL29	ENST00000648640.1		c.213G>C	p.Lys71Asn	missense	Exon 4 of 4	ENSP00000497923.1	A0A3B3ITT5
	RPL29	ENST00000466397.5	TSL:2	c.189G>C	p.Lys63Asn	missense	Exon 4 of 4	ENSP00000418868.1	P47914

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152200 Hom.: 0 Cov.: 32

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000425 AC: 1 AN: 235180 AF XY: 0.00000780

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000906

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000414 AC: 6 AN: 1448058 Hom.: 0 Cov.: 32 AF XY: 0.00000416 AC XY: 3 AN XY: 720592

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111320

Other (OTH) AF: 0.00 AC: 0 AN: 60250

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.79	D
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.060
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.18
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.22	B
Vest4		0.82
MutPred		0.34		Gain of glycosylation at S66 (P = 0.0194)
MVP		0.68
MPC		1.5
ClinPred		0.70	D
GERP RS		2.9
Varity_R		0.26
gMVP		0.35
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs754547606; hg19: chr3-52028056;