dbSNP rs1328974368: RPL28:c.*3249C>A (chr19-55391581-C-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_001136135.2(RPL28):c.352C>A(p.Leu118Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,395,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign 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: 0.0000029 ( 0 hom. )

Consequence

RPL28
NM_001136135.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.371

Variant links:

Genes affected

RPL28 (HGNC:10330): (ribosomal protein L28) 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 60S subunit. The protein belongs to the L28E family of ribosomal proteins. 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. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2008]

RPL28 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=0.07727906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL28	NM_000991.5 link	c.*3249C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000344063.7	NP_000982.2	P46779-1
RPL28	NM_001136135.2 link	c.352C>A	p.Leu118Ile	missense_variant	Exon 5 of 5		NP_001129607.1	P46779-3
RPL28	NM_001136134.1 link	c.*3365C>A		3_prime_UTR_variant	Exon 4 of 4		NP_001129606.1	P46779-2
RPL28	NM_001363697.1 link	c.324+3533C>A		intron_variant	Intron 4 of 4		NP_001350626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RPL28	ENST00000344063.7 link	c.*3249C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000991.5	ENSP00000342787.3	P46779-1
RPL28	ENST00000426763.3 link	n.5101C>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
RPL28	ENST00000558815.5 link	c.352C>A	p.Leu118Ile	missense_variant	Exon 5 of 5	2		ENSP00000452909.1	P46779-3
RPL28	ENST00000560055.5 link	c.324+3533C>A		intron_variant	Intron 4 of 4	3		ENSP00000452763.1	H0YKD8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1395342

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

687552

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:

0.00000372

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000313

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.1

DANN

Benign

0.96

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.22

M_CAP

Benign

0.0028

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.29

Sift

Uncertain

0.0050

Sift4G

Benign

0.076

Vest4

0.093

MVP

0.63

MPC

0.84

ClinPred

0.10

GERP RS

-1.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over