16-1947002-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_005061.3(RPL3L):āc.785T>Cā(p.Val262Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,611,740 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 (ā ).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 34)
Exomes š: 0.00023 ( 0 hom. )
Consequence
RPL3L
NM_005061.3 missense
NM_005061.3 missense
Scores
11
6
2
Clinical Significance
Conservation
PhyloP100: 9.27
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.897
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL3L | NM_005061.3 | c.785T>C | p.Val262Ala | missense_variant | 6/10 | ENST00000268661.8 | |
RPL3L | XM_011522571.3 | c.800T>C | p.Val267Ala | missense_variant | 6/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL3L | ENST00000268661.8 | c.785T>C | p.Val262Ala | missense_variant | 6/10 | 1 | NM_005061.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152224Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000843 AC: 21AN: 249106Hom.: 0 AF XY: 0.0000814 AC XY: 11AN XY: 135168
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GnomAD4 exome AF: 0.000234 AC: 341AN: 1459516Hom.: 0 Cov.: 32 AF XY: 0.000211 AC XY: 153AN XY: 726036
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GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152224Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 11AN XY: 74364
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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 | Aug 06, 2021 | The c.785T>C (p.V262A) alteration is located in exon 6 (coding exon 6) of the RPL3L gene. This alteration results from a T to C substitution at nucleotide position 785, causing the valine (V) at amino acid position 262 to be replaced by an alanine (A). 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
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
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