19-55386389-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000991.5(RPL28):c.32G>A(p.Arg11Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 0 hom. )
Consequence
RPL28
NM_000991.5 missense
NM_000991.5 missense
Scores
3
8
7
Clinical Significance
Conservation
PhyloP100: 8.90
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome4 at 63 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL28 | NM_000991.5 | c.32G>A | p.Arg11Gln | missense_variant | 2/5 | ENST00000344063.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL28 | ENST00000344063.7 | c.32G>A | p.Arg11Gln | missense_variant | 2/5 | 1 | NM_000991.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250968Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135814
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GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 727194
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
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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 | Jan 26, 2022 | The c.32G>A (p.R11Q) alteration is located in exon 2 (coding exon 1) of the RPL28 gene. This alteration results from a G to A substitution at nucleotide position 32, causing the arginine (R) at amino acid position 11 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M;.;M;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
P;.;.;.;.;.;P;.;.
Vest4
MVP
MPC
0.81
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at