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19-55391665-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000991.5(RPL28):c.*3333G>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 0.00000777 in 1,544,114 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

RPL28
NM_000991.5 3_prime_UTR

Scores

1
13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.184
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04017642).
BP6
Variant 19-55391665-G-A is Benign according to our data. Variant chr19-55391665-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2261599.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL28NM_000991.5 linkuse as main transcriptc.*3333G>A 3_prime_UTR_variant 5/5 ENST00000344063.7
RPL28NM_001136135.2 linkuse as main transcriptc.436G>A p.Asp146Asn missense_variant 5/5
RPL28NM_001136134.1 linkuse as main transcriptc.*3449G>A 3_prime_UTR_variant 4/4
RPL28NM_001363697.1 linkuse as main transcriptc.324+3617G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL28ENST00000344063.7 linkuse as main transcriptc.*3333G>A 3_prime_UTR_variant 5/51 NM_000991.5 P1P46779-1
RPL28ENST00000426763.3 linkuse as main transcriptn.5185G>A non_coding_transcript_exon_variant 2/21
RPL28ENST00000558815.5 linkuse as main transcriptc.436G>A p.Asp146Asn missense_variant 5/52 P46779-3
RPL28ENST00000560055.5 linkuse as main transcriptc.324+3617G>A intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000198
AC:
3
AN:
151710
Hom.:
0
AF XY:
0.0000248
AC XY:
2
AN XY:
80686
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000811
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:
0.0000174
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000287
AC:
4
AN:
1391916
Hom.:
0
Cov.:
28
AF XY:
0.00000437
AC XY:
3
AN XY:
686500
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000561
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:
0.00000187
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsNov 15, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
1.5
DANN
Benign
0.42
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0021
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.040
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
0.22
N
Sift
Benign
1.0
T
Vest4
0.092
MVP
0.26
MPC
0.57
ClinPred
0.013
T
GERP RS
-0.0059

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.

Other links and lift over

dbSNP: rs1029256197; hg19: chr19-55903033; API