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GeneBe

19-55391581-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000991.5(RPL28):c.*3249C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,547,524 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RPL28
NM_000991.5 3_prime_UTR

Scores

4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.08663553).
BS2
High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL28NM_000991.5 linkuse as main transcriptc.*3249C>T 3_prime_UTR_variant 5/5 ENST00000344063.7
RPL28NM_001136135.2 linkuse as main transcriptc.352C>T p.Leu118Phe missense_variant 5/5
RPL28NM_001136134.1 linkuse as main transcriptc.*3365C>T 3_prime_UTR_variant 4/4
RPL28NM_001363697.1 linkuse as main transcriptc.324+3533C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL28ENST00000344063.7 linkuse as main transcriptc.*3249C>T 3_prime_UTR_variant 5/51 NM_000991.5 P1P46779-1
RPL28ENST00000426763.3 linkuse as main transcriptn.5101C>T non_coding_transcript_exon_variant 2/21
RPL28ENST00000558815.5 linkuse as main transcriptc.352C>T p.Leu118Phe missense_variant 5/52 P46779-3
RPL28ENST00000560055.5 linkuse as main transcriptc.324+3533C>T intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152182
Hom.:
0
Cov.:
33
show subpopulations
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000108
AC:
15
AN:
1395342
Hom.:
0
Cov.:
30
AF XY:
0.0000145
AC XY:
10
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:
0.0000139
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152182
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsAug 17, 2021The c.352C>T (p.L118F) alteration is located in exon 5 (coding exon 4) of the RPL28 gene. This alteration results from a C to T substitution at nucleotide position 352, causing the leucine (L) at amino acid position 118 to be replaced by a phenylalanine (F). 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
-0.28
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
1.2
DANN
Uncertain
0.99
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.25
T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.087
T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-2.8
D
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0070
D
Vest4
0.091
MVP
0.51
MPC
1.2
ClinPred
0.23
T
GERP RS
-1.4

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: rs1328974368; hg19: chr19-55902949; API