15-66501500-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP3BP4BS2
The NM_000968.4(RPL4):āc.551A>Gā(p.Tyr184Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000508 in 1,614,170 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 (ā ).
Frequency
Genomes: š 0.000059 ( 0 hom., cov: 32)
Exomes š: 0.000050 ( 0 hom. )
Consequence
RPL4
NM_000968.4 missense
NM_000968.4 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 6.05
Genes affected
RPL4 (HGNC:10353): (ribosomal protein L4) 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 L4E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Eigen, MutationAssessor, PrimateAI, PROVEAN [when max_spliceai, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.414045).
BS2
?
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL4 | NM_000968.4 | c.551A>G | p.Tyr184Cys | missense_variant | 6/10 | ENST00000307961.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL4 | ENST00000307961.11 | c.551A>G | p.Tyr184Cys | missense_variant | 6/10 | 1 | NM_000968.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152222Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 250862Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135814
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GnomAD4 exome AF: 0.0000499 AC: 73AN: 1461830Hom.: 0 Cov.: 33 AF XY: 0.0000481 AC XY: 35AN XY: 727220
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152340Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74490
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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 | Oct 05, 2023 | The c.551A>G (p.Y184C) alteration is located in exon 6 (coding exon 6) of the RPL4 gene. This alteration results from a A to G substitution at nucleotide position 551, causing the tyrosine (Y) at amino acid position 184 to be replaced by a cysteine (C). 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
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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