16-1946719-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005061.3(RPL3L):c.857G>A(p.Arg286His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,612,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000048 ( 0 hom. )
Consequence
RPL3L
NM_005061.3 missense
NM_005061.3 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 2.67
Genes affected
RPL3L (HGNC:10351): (ribosomal protein L3 like) This gene encodes a protein that shares sequence similarity with ribosomal protein L3. The protein belongs to the L3P family of ribosomal proteins. Unlike the ubiquitous expression of ribosomal protein genes, this gene has a tissue-specific pattern of expression, with the highest levels of expression in skeletal muscle and heart. It is not currently known whether the encoded protein is a functional ribosomal protein or whether it has evolved a function that is independent of the ribosome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.81
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL3L | NM_005061.3 | c.857G>A | p.Arg286His | missense_variant | 7/10 | ENST00000268661.8 | |
RPL3L | XM_011522571.3 | c.872G>A | p.Arg291His | missense_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL3L | ENST00000268661.8 | c.857G>A | p.Arg286His | missense_variant | 7/10 | 1 | NM_005061.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152278Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000882 AC: 22AN: 249306Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135320
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GnomAD4 exome AF: 0.0000479 AC: 70AN: 1460066Hom.: 0 Cov.: 33 AF XY: 0.0000496 AC XY: 36AN XY: 726318
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152278Hom.: 0 Cov.: 34 AF XY: 0.000121 AC XY: 9AN XY: 74398
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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 | May 30, 2023 | The c.857G>A (p.R286H) alteration is located in exon 7 (coding exon 7) of the RPL3L gene. This alteration results from a G to A substitution at nucleotide position 857, causing the arginine (R) at amino acid position 286 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
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