Variant 19-55391735-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000991.5(RPL28):c.*3403C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000876 in 1,506,924 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 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

RPL28
NM_000991.5 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.390

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011475712).

BS2

High AC in GnomAd4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RPL28	NM_000991.5 linkuse as main transcript	c.*3403C>A		3_prime_UTR_variant	5/5	ENST00000344063.7
RPL28	NM_001136135.2 linkuse as main transcript	c.506C>A	p.Ser169Tyr	missense_variant	5/5
RPL28	NM_001136134.1 linkuse as main transcript	c.*3519C>A		3_prime_UTR_variant	4/4
RPL28	NM_001363697.1 linkuse as main transcript	c.324+3687C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL28	ENST00000344063.7 linkuse as main transcript	c.*3403C>A		3_prime_UTR_variant	5/5	1	NM_000991.5	P1	P46779-1
RPL28	ENST00000426763.3 linkuse as main transcript	n.5255C>A		non_coding_transcript_exon_variant	2/2	1
RPL28	ENST00000558815.5 linkuse as main transcript	c.506C>A	p.Ser169Tyr	missense_variant	5/5	2			P46779-3
RPL28	ENST00000560055.5 linkuse as main transcript	c.324+3687C>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000625

AC:

AN:

144066

Hom.:

AF XY:

0.0000521

AC XY:

AN XY:

76726

show subpopulations

Gnomad AFR exome

AF:

0.000826

Gnomad AMR exome

AF:

0.0000445

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000360

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000613

AC:

AN:

1354794

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

661766

show subpopulations

Gnomad4 AFR exome

AF:

0.000586

Gnomad4 AMR exome

AF:

0.0000297

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:

0.0000555

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

AF:

0.000322

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00109

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000595

Hom.:

Bravo

AF:

0.000332

ESP6500AA

AF:

0.00217

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000230

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.506C>A (p.S169Y) alteration is located in exon 5 (coding exon 4) of the RPL28 gene. This alteration results from a C to A substitution at nucleotide position 506, causing the serine (S) at amino acid position 169 to be replaced by a tyrosine (Y). 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

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.58

CADD

Benign

3.0

DANN

Benign

0.82

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.28

M_CAP

Benign

0.0022

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.060

Sift

Pathogenic

0.0

Vest4

0.20

MVP

0.19

MPC

0.75

ClinPred

0.014

GERP RS

-1.8

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over