Variant 19-55391605-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_001136135.2(RPL28):c.376C>A(p.Pro126Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,396,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

RPL28
NM_001136135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0320

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:

RPL28 (HGNC:):

RPL28 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05985853).

BS2

High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL28	NM_000991.5 linkuse as main transcript	c.*3273C>A		3_prime_UTR_variant	5/5	ENST00000344063.7	NP_000982.2	P46779-1
RPL28	NM_001136135.2 linkuse as main transcript	c.376C>A	p.Pro126Thr	missense_variant	5/5		NP_001129607.1	P46779-3
RPL28	NM_001136134.1 linkuse as main transcript	c.*3389C>A		3_prime_UTR_variant	4/4		NP_001129606.1	P46779-2
RPL28	NM_001363697.1 linkuse as main transcript	c.324+3557C>A		intron_variant			NP_001350626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RPL28	ENST00000344063.7 linkuse as main transcript	c.*3273C>A		3_prime_UTR_variant	5/5	1	NM_000991.5	ENSP00000342787.3	P46779-1
RPL28	ENST00000426763.3 linkuse as main transcript	n.5125C>A		non_coding_transcript_exon_variant	2/2	1
RPL28	ENST00000558815.5 linkuse as main transcript	c.376C>A	p.Pro126Thr	missense_variant	5/5	2		ENSP00000452909.1	P46779-3
RPL28	ENST00000560055.5 linkuse as main transcript	c.324+3557C>A		intron_variant		3		ENSP00000452763.1	H0YKD8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000132

AC:

AN:

151568

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80590

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000349

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000229

AC:

AN:

1396822

Hom.:

Cov.:

AF XY:

0.0000247

AC XY:

AN XY:

688842

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:

0.0000297

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000424

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

Apr 08, 2024

The c.376C>A (p.P126T) 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 376, causing the proline (P) at amino acid position 126 to be replaced by a threonine (T). 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

-0.35

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.99

DANN

Uncertain

0.98

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.32

M_CAP

Benign

0.0021

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.72

Sift

Benign

0.097

Sift4G

Benign

0.10

Vest4

0.094

MVP

0.30

MPC

0.74

ClinPred

0.029

GERP RS

0.89

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